Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders

ABSTRACT

Corticotropin releasing factor (CRF) antagonists of formula (I):                    
     and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a divisional of U.S. Ser. No. 09/208,778 filed Dec. 10, 1998,now U.S. Pat. No. 6,362,180 issued Mar. 26, 2002, which is acontinuation of U.S. Ser. No. 09/109,877 filed Jul. 2, 1998, now U.S.Pat. No. 6,143,743 issued Nov. 7, 2000, which claims the benefit of U.S.Provisional Application No. 60/080,665 filed Apr. 3, 1998 and U.S.Provisional Application No. 60/051,628 filed Jul. 3, 1997.

FIELD OF THE INVENTION

The present invention relates to novel compounds, compositions, andmethods for the treatment of psychiatric disorders and neurologicaldiseases, including major depression, anxiety-related disorders,post-traumatic stress disorder, supranuclear palsy and feedingdisorders, as well as treatment of immunological, cardiovascular orheart-related diseases and colonic hypersensitivity associated withpsychopathological disturbance and stress. In particular, the presentinvention relates to novel imidazopyrimidines and imidazopyridines,pharmaceutical compositions containing such compounds and their use intreating psychiatric disorders, neurological diseases, immunological,cardiovascular or heart-related diseases and colonic hypersensitivityassociated with psychopathological disturbance and stress.

BACKGROUND OF THE INVENTION

Corticotropin releasing factor (herein referred to as CRF), a 41 aminoacid peptide, is the primary physiological regulator ofproopiomelanocortin (POMC)—derived peptide secretion from the anteriorpituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851(1983); W. Vale et al., Science 213:1394 (1981)]. In addition to itsendocrine role at the pituitary gland, immunohistochemical localizationof CRF has demonstrated that the hormone has a broad extrahypothalamicdistribution in the central nervous system and produces a wide spectrumof autonomic, electrophysiological and behavioral effects consistentwith a neurotransmitter or neuromodulator role in brain [W. Vale et al.,Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39(1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There isalso evidence that CRF plays a significant role in integrating theresponse of the immune system to physiological, psychological, andimmunological stressors [J. E. Blalock, Physiological Reviews 69:1(1989); J. E. Morley, Life Sci. 41:527 (1987)].

Clinical data provide evidence that CRF has a role in sychiatricdisorders and neurological diseases including depression,anxiety-related disorders and feeding disorders. A role for CRF has alsobeen postulated in the etiology and pathophysiology of Alzheimer'sdisease, Parkinson's disease, Huntington's disease, progressivesupranuclear palsy and amyotrophic lateral sclerosis as they relate tothe dysfunction of CRF neurons in the central nervous system [for reviewsee E. B. De Souza, Hosp. Practice 23:59 (1988)].

In affective disorder, or major depression, the concentration of CRF issignificantly increased in the cerebral spinal fluid (CSF) of drug-freeindividuals [C. B. Nemeroff et al., Science 226:1342 (1984); C. M. Bankiet al., Am. J. Psychiatry 144:873 (1987); R. D. France et al., Biol.Psychiatry 28:86 (1988); M. Arato et al., Biol Psychiatry 25:355(1989)]. Furthermore, the density of CRF receptors is significantlydecreased in the frontal cortex of suicide victims, consistent with ahypersecretion of CRF [C. B. Nemeroff et al., Arch. Gen. Psychiatry45:577 (1988)]. In addition, there is a blunted adrenocorticotropin(ACTH) response to CRF (i.v. administered) observed in depressedpatients [P. W. Gold et al., Am J. Psychiatry 141:619 (1984); F.Holsboer et al., Psychoneuroendocrinology 9:147 (1984); P. W. Gold etal., New Eng. J. Med. 314:1129 (1986)]. Preclinical studies in rats andnon-human primates provide additional support for the hypothesis thathypersecretion of CRF may be involved in the symptoms seen in humandepression [R. M. Sapolsky, Arch. Gen. Psychiatry 46:1047 (1989)]. Thereis preliminary evidence that tricyclic antidepressants can alter CRFlevels and thus modulate the numbers of CRF receptors in brain[Grigoriadis et al., Neuropsychopharmacology 2:53 (1989)].

It has also been postulated that CRF has a role in the etiology ofanxiety-related disorders. CRF produces anxiogenic effects in animalsand interactions between benzodiazepine/non-benzodiazepine anxiolyticsand CRF have been demonstrated in a variety of behavioral anxiety models[D. R. Britton et al., Life Sci. 31:363 (1982); C. W. Berridge and A. J.Dunn Regul. Peptides 16:83 (1986)]. Preliminary studies using theputative CRF receptor antagonist a-helical ovine CRF (9-41) in a varietyof behavioral paradigms demonstrate that the antagonist produces“anxiolytic-like” effects that are qualitatively similar to thebenzodiazepines [C. W. Berridge and A. J. Dunn Horm. Behav. 21:393(1987), Brain Research Reviews 15:71 (1990)].

Neurochemical, endocrine and receptor binding studies have alldemonstrated interactions between CRF and benzodiazepine anxiolytics,providing further evidence for the involvement of CRF in thesedisorders. Chlordiazepoxide attenuates the “anxiogenic” effects of CRFin both the conflict test [K. T. Britton et al., Psychopharmacology86:170 (1985); K. T. Britton et al., Psychopharmacology 94:306 (1988)]and in the acoustic startle test [N. R. Swerdlow et al.,Psychopharmacology 88:147 (1986)] in rats.

The benzodiazepine receptor antagonist (Ro15-1788), which was withoutbehavioral activity alone in the operant conflict test, reversed theeffects of CRF in a dose-dependent manner while the benzodiazepineinverse agonist (FG7142) enhanced the actions of CRF [K. T. Britton etal., Psychopharmacology 94:306 (1988)].

It has been further postulated that CRF has a role in immunological,cardiovascular or heart-related diseases such as hypertension,tachycardia and congestive heart failure, stroke, osteoporosis,premature birth, psychosocial dwarfism, stress-induced fever, ulcer,diarrhea, post-operative ileus and colonic hypersensitivity associatedwith psychopathological disturbance and stress.

The mechanisms and sites of action through which the standardanxiolytics and antidepressants produce their therapeutic effects remainto be elucidated. It has been hypothesized however, that they areinvolved in the suppression of the CRF hypersecretion that is observedin these disorders. Of particular interest is that preliminary studiesexamining the effects of a CRF receptor antagonist (a-helical CRF9-41)in a variety of behavioral paradigms have demonstrated that the CRFantagonist produces “anxiolytic-like” effects qualitatively similar tothe benzodiazepines (for review see G. F. Koob and K. T. Britton, In:Corticotropin-Releasing Factor: Basic and Clinical Studies of aNeuropeptide, E. B. De Souza and C. B. Nemeroff eds., CRC Press p221(1990)).

DuPont Merck PCT application US94/11050 describes corticotropinreleasing factor antagonist compounds of the formula:

and their use to treat psychiatric disorders and neurological diseases.Included in the description are fused pyridines and pyrimidines of theformula:

where: V is CR^(1a) or N; Z is CR² or N; A is CR³O or N; and D is CR² orN.

Other compounds reported to have activity as corticotropin releasingfactors are disclosed in WO 95/33750, WO 95/34563 and WO 95/33727.

SUMMARY OF THE INVENTION

In accordance with one aspect, the present invention provides novelcompounds which bind to corticotropin releasing factor receptors,thereby altering the anxiogenic effects of CRF secretion. The compoundsof the present invention are useful for the treatment of psychiatricdisorders and neurological diseases, anxiety-related disorders,post-traumatic stress disorder, supranuclear palsy and feeding disordersas well as treatment of immunological, cardiovascular or heart-relateddiseases and colonic hypersensitivity associated with psychopathologicaldisturbance and stress in mammals.

According to another aspect, the present invention provides novelcompounds of formula (I) (described below) which are useful asantagonists of the corticotropin releasing factor. The compounds of thepresent invention exhibit activity as corticotropin releasing factorantagonists and appear to suppress CRF hypersecretion. The presentinvention also includes pharmaceutical compositions containing suchcompounds of formula (I), and methods of using such compounds for thesuppression of CRF hypersecretion, and/or for the treatment ofanxiogenic disorders.

According to yet another aspect, the present invention provides novelcompounds, pharmaceutical compositions and methods which may be used inthe treatment of affective disorder, anxiety, depression, irritablebowel syndrome, post-traumatic stress disorder, supranuclear palsy,immune suppression, Alzheimer's disease, gastrointestinal disease,anorexia nervosa or other feeding disorder, drug or alcohol withdrawalsymptoms, drug addiction, inflammatory disorder, fertility problems,disorders, the treatment of which can be effected or facilitated byantagonizing CRF, including but not limited to disorders induced orfacilitated by CRF, or a disorder selected from inflammatory disorderssuch as rheumatoid arthritis and osteoarthritis, pain, asthma, psoriasisand allergies; generalized anxiety disorder; panic, phobias,obsessive-compulsive disorder; post-traumatic stress disorder; sleepdisorders induced by stress; pain perception such as fibromyalgia; mooddisorders such as depression, including major depression, single episodedepression, recurrent depression, child abuse induced depression, andpostpartum depression; in dysthemia; bipolar disorders; cyclothymia;fatigue syndrome; stress-induced headache; cancer, humanimmunodeficiency virus (HIV) infections; neurodegenerative diseases suchas Alzheimer's disease, Parkinson's disease and Huntington's disease;gastrointestinal diseases such as ulcers, irritable bowel syndrome,Crohn's disease, spastic colon, diarrhea, and post operative ilius andcolonic hypersensitivity associated by psychopathological disturbancesor stress; eating disorders such as anorexia and bulimia nervosa;hemorrhagic stress; stress-induced psychotic episodes; euthyroid sicksyndrome; syndrome of inappropriate antidiarrhetic hormone (ADH);obesity; infertility; head traumas; spinal cord trauma; ischemicneuronal damage (e.g., cerebral ischemia such as cerebral hippocampalischemia); excitotoxic neuronal damage; epilepsy; cardiovascular andhear related disorders including hypertension, tachycardia andcongestive heart failure; stroke; immune dysfunctions including stressinduced immune dysfunctions (e.g., stress induced fevers, porcine stresssyndrome, bovine shipping fever, equine paroxysmal fibrillation, anddysfunctions induced by confinement in chickens, sheering stress insheep or human-animal interaction related stress in dogs); muscularspasms; urinary incontinence; senile dementia of the Alzheimer's type;multiinfarct dementia; amyotrophic lateral sclerosis; chemicaldependencies and addictions (e.g., dependencies on alcohol, cocaine,heroin, benzodiazepines, or other drugs); drug and alcohol withdrawalsymptoms; osteoporosis; psychosocial dwarfism and hypoglycemia inmammals.

According to a still further aspect of the invention, the compoundsprovided by this invention (and especially labelled compounds of thisinvention) are also useful as standards and reagents in determining theability of a potential pharmaceutical to bind to the CRF receptor.

DETAILED DESCRIPTION OF INVENTION

[1] Thus, in a first embodiment, the present invention provides a novelcompound of formula I:

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein:

A is N or C—R⁷;

B is N or C—R⁸;

provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbonatom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl,—SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a),—NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), C₁₋₄ alkoxy-C₁₋₄ alkyl, and C₃₋₈ cycloalkyl which issubstituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl isreplaced by —O—;

provided that R¹ is other than:

(a) a cyclohexyl-(CH₂)₂— group;

(b) a 3-cyclopropyl-3-methoxypropyl group;

(c) an unsubstituted-(alkoxy)methyl group; and,

(d) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbonadjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), C₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl, —(CH₂)₁₋₄-heteroaryl,or —(CH₂)₁₋₄-heterocycle, wherein the aryl, heteroaryl, or heterocyclegroup is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl,and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected fromthe group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from thegroup —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from thegroup H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy,C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substitutedwith 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br,Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy<, C₁₋₄alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and(C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is otherthan substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the groupH, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)— and benzyl,each benzyl being substituted on the aryl moiety with 0-1 substituentsselected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro,C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl andbenzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl,nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence from the groupH, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalky;

alternatively, In an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) takentogether form 1-pyrrolidinyl, 1-norpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl,naphthyl, indanyl and indenyl, each aryl being substituted with 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy,—OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹,—NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenylsubstituent being substituted with 0-4 substituents selected from thegroup C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃,C₂F₅, OCF₃, SC₂Me and acetyl;

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl,benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a); and,

provided that when D is imidazole or triazole, R¹ is other thanunsubstituted C₁₋₆ linear or branched alkyl or C₃₋₆ cycloalkyl.

[2] In a preferred embodiment, the present invention provides a novelcompound of formula Ia:

[2a] In a more preferred embodiment, the present invention provides anovel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a), —NCO₂R^(14b), —NCOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R³ and R⁸ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2b] In an even more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a);

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SQ₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2c] In a still more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂CH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2d] In a further preferred embodiment, the present invention provides anovel compound of formula Ia, wherein:

R¹ is substituted (cyclopropyl)—C₁ alkyl or (cyclobutyl)—C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂OH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2e] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)—C₁ alkyl substituted with 1substituent independently selected at each occurrence from the groupR^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂,—CH═CH(CH₃), —CH≡—CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃,cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atomswith a substituent independently selected at each occurrence from thegroup CH₃, OCH₃, Cl, F, and CF₃.

[2f] In an even further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃,(cyclopropyl)CH—CH₂CH₃, (cyclpropyl)CH—CH₂OCH₃,(cyclopropyl)CH—CH₂CH₂CH₃, (cycloppropyl)CH—CH₂OCH₃, (cyclopropyl)₂CH,phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH,isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH,(cyclobutyl)CH—CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)CH—CH₂OCH₃,(cyclobutyl)CH—CH₂CH₂CH₃, (cyclobutyl)CH—CH₂CH₂OCH₃, (cyclobutyl)₂CH,phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH,isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH;

[2g] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[2h] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[2i] In another preferred embodiment, the present invention provides anovel compound of formula Ia, wherein the compound is selected from thegroup:

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-[2-methyl-4-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-2-methoxy-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;

3-chloro-4-[3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;

1-{3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

3-(dicyclopropylmethyl)-2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(dicyclopropylmethyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

1-{3-chloro-4-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{5-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-{5-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-methoxy-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-methoxy-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;and

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

or a pharmaceutically acceptable salt form thereof.

[2j]In another more preferred embodiment, the present invention providesa novel compound of formula Ia, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—,—NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[2k] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, whereinone carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl,and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ and R⁸ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁶, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2l] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃,—CH₂OCH₃, CH₂CH₂OCH₃, and NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2m] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, CH═CH(CH₃), —CH≡CH, —CH≡—C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituentsindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2n] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,—(CH₂)₃CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2o] In a still further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[2p] In another still further preferred embodiment, the presentinvention provides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[2q] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₈ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and—NSO₂R^(14b)—;

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which issubstituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl isreplaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂—,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized.

[2r] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,and C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₆ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ and R⁸ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2s] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms inthe C₄₋₆ cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂OCH₃, CH₂CH₂OCH₃and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCH₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2t] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2u] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2v] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[2w] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[3] In another preferred embodiment, the present invention provides anovel compound of formula Ib:

[3a] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R³ and R⁷ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OCO(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[3b] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁷ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3c] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, CO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3d] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is substituted (cyclopropyl)—C₁ alkyl or (cyclobutyl)—C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), Br, Cl,F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R¹ is also substituted with 0-1 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂CH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3e] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)—C₁ alkyl substituted with 1substituent independently selected at each occurrence from the groupR^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂,—CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃,cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atomswith a substituent independently selected at each occurrence from thegroup CH₃, OCH₃, Cl, F, and CF₃.

[3f] In an even further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃,(cyclopropyl)CH—CH₂CH₃, (cyclopropyl)CH—CH₂OCH₃,(cyclopropyl)CH—CH₂CH₂CH₃, (cyclopropyl)CH—CH₂CH₂OCH₃, (cyclopropyl)₂CH,phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH,isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH,(cyclobutyl)CH—CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)CH—CH₂OCH₃,(cyclobutyl)CH—CH₂CH₂CH₃, (cyclobutyl)CH—CH₂CH₂OCH₃, (cyclobutyl)₂CH,phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH,isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH.

[3g] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[3h] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[3i] In another preferred embodiment, the present invention provides anovel compound of formula Ib, wherein the compound is selected from thegroup:

1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-[2-methyl-4-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-(methylsulfanyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

2,4-(2-chloro-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-methoxy-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-2-methoxy-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;

3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;

1-{3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;.

1-{3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-(dicyclopropylmethyl)-2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(dicyclopropylmethyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

1-{3-chloro-4-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-{5-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-{5-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-methoxy-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-[1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-methoxy-1-[1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;and

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

or a pharmaceutically acceptable salt form thereof.

[3j] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—,—NCO₂R^(14b)—NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[3k] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, whereinone carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a)—, NCO₂R^(14b)—, NCOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl,and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ and R⁷ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[3l] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a—;)

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃,—CH₂OCH₃, —CH₂CH₂OCH₃, and —NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃; R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

R³ and R⁷ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3m] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂OH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituentsindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3n] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,—(CH₂)₃CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3o] In another still further preferred embodiment, the presentinvention provides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[3p] In another still further preferred embodiment, the presentinvention provides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[3q] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₈ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, —NR^(13a), —NCO₂R^(14b), —NCOR^(14b)— andSO₂R^(14b)—.

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), C₁₋₂ alkoxyC₁₋₂ alkyl, and C₃₋₈ cycloalkyl which issubstituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl isreplaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized.

[3r] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₆ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and R^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ and R⁷ are independently selected at each occurrence from the groupH, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR^(15COR) ¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a);

[3s] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms inthe C₄₋₄ cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂CH₃, —CH₂CH₂OCH₃,and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁷ are independently selected at each occurrence from the groupH, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂OH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3t] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group Hand CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3u] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3v] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[3w] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[4] In another preferred embodiment, the present invention provides anovel compound of formula Ic:

[4a] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b), —NCOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,NR^(17a)R^(19a), and —CONR^(17a)R¹⁹a and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(n)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[4b] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₂alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and inwhich 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4c] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN,—CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂OH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₀₂CH₃, COCH₃ andSO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroarylwherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4d] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is substituted (cyclopropyl)—C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂OH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4e] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)—C₁ alkyl substituted with 1substituent independently selected at each occurrence from the groupR^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂,—CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂,CH₃, —CH₂CH₂OCH₃, F, CF₃,cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atomswith a substituent independently selected at each occurrence from thegroup CH₃, OCH₃, Cl, F, and CF₃.

[4f] In an even further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃,(cyclopropyl)CH—CH₂CH₃, (cyclopropyl)CH—CH₂OCH₃,(cyclopropyl)CH—CH₂CH₂CH₃, (cyclopropyl)CH—CH₂CH₂OCH₃, (cyclopropyl)₂CH,phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH,isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH,(cyclobutyl)CH—CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)CH—CH₂OCH₃,(cyclobutyl)CH—CH₂CH₂CH₃, (cyclobutyl)CH—OH₂C₂OCH₃, (cyclobutyl)₂CH,phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH,isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH.

[4g] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[4h] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[4i] In another preferred embodiment, the present invention provides anovel compound of formula Ic, wherein the compound is selected from thegroup:

6-(2,4-bis(trifluoromethyl)phenyl-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-cyanophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxy-5-chlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxy-5-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-hexyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-heptyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2-chloro-4-methyl-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-methylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-methylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-3-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-hexyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[(2-furanyl)-cyclopropylmethyl]-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[1-(2-furanyl)propyl]-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclobutylethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-butynyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-propenyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-[1-cyclopropyl-1-(2-thienyl)methyl]-8-ethyl-9H-purine;

9-(1-cyclobutylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-[1-cyclopropyl-(3-methylisoxazol-5-yl)methyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propynyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropyl-4′-fluorobenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbenzyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylpentyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylpropyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylpropyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylpropyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;

9-(1-cyclopropylpropyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

6-(2,4-dichloro-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;

6-(2,4-dichloro-6-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-methoxycarbonylpropyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyn-4-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(3-heptyl)-9H-purine;

6-(2,4-.dichlorophenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(3-pentyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-[1-(2-methylcyclopropyl)ethyl]-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2,4-dichlorophenyl)-9-(diphenylmethyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,6-dimethoxypyridin-3-yl)-8-methoxy-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2,4,5-trichlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methoxy-4-trifluoromethylphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-dimethylaminophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-fluorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-chloro-4-methoxy-5-fluorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-propyloxyphenyl)-9H-purine;

6-(2,6-dimethoxypyridin-3-yl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2,4-dimethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(2-pentyl)-9H-purine;

8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(3-pentyl)-9H-purine;

8-ethyl-9-(1-hexen-3-yl)-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

8-ethyl-9-(1-hexen-3-yl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(2-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(2-pentyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-hexyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-pentyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-methyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-b eptyl)-6-(2-trifluoromethyl-4 methoxyphenyl)-9H-purine;and

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-6-methoxy-3-pyridyl)-9H-purine;

or a pharmaceutically acceptable salt form thereof.

[4j] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—,—NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[4k] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, whereinone carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selectedfrom the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)—and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl,and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴,

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[4l] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group C, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN,OC₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃,—OH₂OCH₃, —CH₂CH₂CH₃, and NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(Q)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4m] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituentsindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)_(2, OCH)₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃,—N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4n] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is substituted with 0-2 substituents independently selected at eachoccurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,—(CH₂)₃CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4o] In another still further preferred embodiment, the presentinvention provides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[4p] In another still further preferred embodiment, the presentinvention provides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[4q] In another more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₈ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, —NR^(13a), —NCO₂R^(14b)—, —NCOR^(14b)— and—NSO₂R^(14b)—;

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which issubstituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl isreplaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R,—NR^(17a)R^(19a) and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized.

[4r] In another even more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,and C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atomsin the C₄₋₆ cycloalkyl group is replaced by a group selected from thegroup —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, eachR^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituentsindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl,oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl,each heteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₄ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷,—NR^(17a)R^(19a), and —CONR^(17a)R¹⁹a and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyland is substituted with 0-1 substituents selected from the group —CN,OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄alkyl and C₃₋₈ cycloalkyl;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)—, andheteroaryl(C₁₋₂ alkyl)—;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from thegroup H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selectedat each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷,Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl,indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 1-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a);

[4s] In another still more preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms inthe C₄₋₄ cycloalkyl is replaced by a group selected from the group —O—,—S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl,C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂OCH₃,—CH₂CH₂OCH₃, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ andin which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selectedfrom OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3substituents independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN,SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3carbon atoms with a substituent independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl,OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃,—NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl,each heteroaryl being substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(C)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4t] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl,CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃,OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at eachoccurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F,CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, andtetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with asubstituent independently selected at each occurrence from the groupCH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atomwith 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ andSO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selectedat each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃,—CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and—C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂,—C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4u] In another even further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at eachoccurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃),—CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is-phenyl substituted with 0-2 substituents independentlyselected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl,imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, eachheteroaryl being substituted on 0-3 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4v] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected ateach occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃,cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, andCF₃.

[4w] In another further preferred embodiment, the present inventionprovides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituentindependently selected at each occurrence from the group CH₃, CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃,OCF₃, Br, Cl, F, and CF₃.

[5l] In a third embodiment, the present invention provides a novelpharmaceutical composition, comprising: a pharmaceutically acceptablecarrier arid a therapeutically effective amount of a compound of formula(I):

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein:

A is N or C—R⁷;

B is N or C—R⁸;

provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbonatom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl,—SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—,—NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)— and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than:

(a) a 3-cyclopropyl-3-methoxypropyl group;

(b) an unsubstituted-(alkoxy)methyl group; and,

(c) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbonadjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-5 substituentsindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl,and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected fromthe group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from thegroup —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from thegroup H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy,C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substitutedwith 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br,Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and(C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁ o alkyl, then R³ is otherthan substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the groupH, C₁₋₄ alkyl, C₃₋₈ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)— and benzyl,each benzyl being substituted on the aryl moiety with 0-1 substituentsselected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro,C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl andbenzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl,nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence from the groupH, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, whereinN₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) takentogether form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl,naphthyl, indanyl and indenyl, each aryl being substituted with 0-5substituents independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy,—OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸,—COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹,—NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenylsubstituent being substituted with 0-4 substituents selected from thegroup C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃,C₂F₅, OCF₃, SO₂Me and acetyl; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl,benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[6] In a second embodiment, the present invention provides a novelmethod of treating affective disorder, anxiety, depression, headache,irritable bowel syndrome, post-traumatic stress disorder, supranuclearpalsy, immune suppression, Alzheimer's disease, gastrointestinaldiseases, anorexia nervosa or other feeding disorder, drug addiction,drug or alcohol withdrawal symptoms, inflammatory diseases,cardiovascular or heart-related diseases, fertility problems, humanimmunodeficiency virus infections, hemorrhagic stress, obesity,infertility, head and spinal cord traumas, epilepsy, stroke, ulcers,amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatmentof which can be effected or facilitated by antagonizing CRF, includingbut not limited to disorders induced or facilitated by CRF, in mammals,comprising: administering to the mammal a therapeutically effectiveamount of a compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein:

A is N or C—R⁷;

B is N or C—R⁸;

provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbonatom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl,C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl,—SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN,—S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a),—N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO_(2R) ^(14b),—CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, andC₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl isreplaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a),—NCO₂R^(14b)—, —NCOR¹⁴— and —NSO₂R^(14b)—, and wherein N₄ in1-piperazinyl is substituted with 0-1 substituents selected from thegroup R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected ateach occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a),—NR^(13a)R^(16a), and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than:

(a) a 3-cyclopropyl-3-methoxypropyl group;

(b) an unsubstituted-(alkoxy)methyl group; and,

(c) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbonadjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyland indenyl, each R^(1a) being substituted with 0-5 substituentsindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸,—NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸,—NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl beingsubstituted on any nitrogen atom with 0-1 substituents selected from thegroup R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturatedheteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms witha substituent independently selected at each occurrence from the groupC₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro,—OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b),—NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a),—NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and eachheterocyclyl being substituted on any nitrogen atom with 0-1substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) andSO₂R^(14b) and wherein any sulfur atom is optionally monooxidized ordioxidized;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl,and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected fromthe group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from thegroup —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from thegroup H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy,C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substitutedwith 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br,Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and(C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is otherthan substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the groupH, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)—;

R^(13a) and R^(16a) are independently selected at each occurrence fromthe group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl,aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)— and benzyl,each benzyl being substituted on the aryl moiety with 0-1 substituentsselected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro,C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl andbenzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl,nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H,C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence form the groupH, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein,N₄ in 1-piperazinyl is substituted with 0-1 substituents selected fromthe group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) takentogether form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein, N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl,naphthyl, indanyl and indenyl, each aryl R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;being substituted with 0-5 substituents independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy,C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂,—NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1phenyl, each phenyl substituent being substituted with 0-4 substituentsselected from the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN,dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; and,

heteroaryl is independently selected at each occurrence from the grouppyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl,thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl,benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl,triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl,2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide,2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl,benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷,—OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸,—NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on anynitrogen atom with 0-1 substituents selected from the group R¹⁵,CO₂R^(14a), COR^(14a) and SO₂R^(14a).

In another preferred embodiment, R¹ is other than acyclohexyl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group.

In another preferred embodiment, R¹ is other than anaryl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, wherein the arylgroup is substituted or unsubstituted.

In another preferred embodiment, R¹ is other than aheteroaryl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, wherein theheteroaryl group is substituted or unsubstituted.

In another preferred embodiment, R¹ is other than aheterocyclyl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, whereinthe heterocyclyl group is substituted or unsubstituted.

In another preferred embodiment, when D is imidazole or triazole, R¹ isother than unsubstituted C_(1, 2, 3, 4, 5, 6, 7, 8, 9,) or 10 linear orbranched alkyl or C_(3, 4, 5, 6, 7,) or 8 cycloalkyl.

In another preferred embodiment, R^(1a) is not substituted with OR¹⁷.

Many compounds of this invention have one or more asymmetric centers orplanes. Unless otherwise indicated, all chiral (enantiomeric anddiastereomeric) and racemic forms are included in the present invention.Many geometric isomers of olefins, C═N double bonds, and the like canalso be present in the compounds, and all such stable isomers arecontemplated in the present invention. The compounds may be isolated inoptically active or racemic forms. It is well known in the art how toprepare optically active forms, such as by resolution of racemic formsor by synthesis from optically active starting materials. All chiral,(enantiomeric and diastereomeric) and racemic forms and all geometricisomeric forms of a structure are intended, unless the specificstereochemistry or isomer form is specifically indicated. The term“alkyl” includes both branched and straight-chain alkyl having thespecified number of carbon atoms. “Alkenyl” includes hydrocarbon chainsof either a straight or branched configuration and one or moreunsaturated carbon-carbon bonds which may occur in any stable pointalong the chain, such as ethenyl, propenyl, and the like. “Alkynyl”includes hydrocarbon chains of either a straight or branchedconfiguration and one or more triple carbon-carbon bonds which may occurin any stable point along the chain, such as ethynyl, propynyl and thelike. “Haloalkyl” is intended to include both branched andstraight-chain alkyl having the specified number of carbon atoms,substituted with 1 or more halogen; “alkoxy” represents an alkyl groupof indicated number of carbon atoms attached through an oxygen bridge;“cycloalkyl” is intended to include saturated ring groups, includingmono-,bi- or polycyclic ring systems, such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, and so forth. “Halo” or “halogen, includesfluoro, chloro, bromo, and iodo.

The term 'substituted”, as used herein, means that one or more hydrogenon the designated atom is replaced with a selection from the indicatedgroup, provided that the designated atom's normal valency is notexceeded, and that the substitution results in a stable compound. When asubstitent is keto (i.e., ═O), then 2 hydrogens on the atom arereplaced.

Combinations of substituents and/or variables are permissible only ifsuch combinations result in stable compounds. By “stable compound” or“stable structure” is meant a compound that is sufficiently robust tosurvive isolation to a useful degree of purity from a reaction mixture,and formulation into an efficacious therapeutic agent.

The term “pharmaceutically acceptable salts” includes acid or base saltsof the compounds of formulas (I) and (II). Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like.

Pharmaceutically acceptable salts of the compounds of the invention canbe prepared by reacting the free acid or base forms of these compoundswith a stoichiometric amount of the appropriate base or acid in water orin an organic solvent, or in a mixture of the two; generally, nonaqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Reminaton'sPharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa.,1985, p. 1418, the disclosure of which is hereby incorporated byreference.

“Prodrugs” are considered to be any covalently bonded carriers whichrelease the active parent drug of formula (I) or (II) in vivo when suchprodrug is administered to a mammalian subject. Prodrugs of thecompounds of formula (I) and (II) are prepared by modifying functionalgroups present in the compounds in such a way that the modifications arecleaved, either in routine manipulation or in vivo, to the parentcompounds. Prodrugs include compounds wherein hydroxy, amine, orsulfhydryl groups are abonded to any group that, when administered to amammalian subject, cleaves to form a free hydroxyl, amino, or sulfhydrylgroup, respectively. Examples of prodrugs include, but are not limitedto, acetate, formate and benzoate derivatives of alcohol and aminefunctional groups in the compounds of formulas (I) and (II); and thelike.

The term “therapeutically effective amount” of a compound of thisinvention means an amount effective to antagonize abnormal level of CRFor treat the symptoms of affective disorder, anxiety, depression,immunological, cardiovascular or heart-related diseases and colonichypersensitivity associated with psychopathological disturbance andstress in a host.

SYNTHESIS

Compounds of formula (I) can be prepared by the following syntheticroutes and schemes. Where a detailed description is not provided, it isassumed that those skilled in the art of organic synthesis will readilyunderstand the meaning.

Synthesis of compounds of formula (I) may be prepared by the reactionshown in Scheme 1.

A compound of formula (II) can be alkylated on the imidazole nitrogenatom with an appropriate reagent. Typical conditions for thistransformation include treatment of compound (II) with a base, such assodium hydride, potassium tert-butoxide, sodium hexamethyldisilazide,etc., followed by a reagent J—R¹, where J represents a halide (chloride,bromide or iodide) or psuedohalide (tosylate, mesylate, triflate, etc.),at an appropriate temperature (0° C. or room temperature, with warmingif necessary) in a solvent such as tetrahydrofuran, dimethylformamide ordimethylsulfoxide. Alternatively, this reaction may be performed usingthe Mitsunobu conditions (Mitsunobu, Synthesis 1981, pp. 1-28).Thecompound (II) is treated with an alcohol compound R¹OH, along with aphosphine (triphenyl, tributyl, etc.) and a phosphine-activating reagentsuch as diethyl azodicarboxylate.

Compounds of Formula (II) may be prepared according to the route shownin Scheme 2.

A compound of Formula (III) may be coupled to an aromatic compound ofFormula (IV), with elimination of the elements of M—K. For compound(III), K represents a halide, psuedohalide (such as mesylate, tosylateor triflate), or thiomethyl, and P represents a protecting group (if theconditions of the reaction warrant protection of the imidazole N—H;otherwise, P can be H). Suitable P groups may include benzyl,4-methoxybenzyl, methoxymethyl, trimethylsilylethoxymethyl,tert-butoxycarbonyl or benzyloxycarbonyl. For compound (IV), Mrepresents groups such as lithium, bromomagnesium, chlorozinc,(dihydroxy)boron, (dialkoxy)boron, trialkylstannyl and the like. Thecoupling reaction may be performed in the presence of an appropriatecatalyst, such as tetrakis(triphenylphosphine)palladium,bis(triphenylphosphine)palladium dichloride,[1,3-bis(diphenylphosphino)propane]nickel dichloride, etc. Twoparticularly useful methods involve the coupling of chloroheterocycleswith in-situ-prepared arylzinc reagents according to the method ofNegishi et al. (J. Org. Chem. 1977, 42, 1821), and the coupling witharylboronic esters according to the method of Suzuki et al. (Chem.Letters 1989, 1405). Appropriate solvents for reactions of this typeusually include tetrahydrofuran, diethyl ether, dimethylformamide, ordimethylsulfoxide. Typical temperatures range from ambient up to theboiling point of the solvent. Once coupled, the P group may be removedto afford compound (II). Conditions for the removal of the protectinggroups are well known to those familiar to the art of organic synthesis;e.g. hydrogenation to remove benzyl or benzyloxycarbonyl, a fluoridesource (such as tetrabutylammonium fluoride) to removesilylethoxymethyl, an acid source (such as trifluoroacetic acid) toremove tert-butoxycarbonyl or 4-methoxybenzyl, etc.

Compounds of formula (III) can be prepared according to the plan shownin Scheme 3.

A diamine compound of formula (V) (in this case, P is a group such asbenzyl, which can be introduced already attached to the nitrogen atom;otherwise, P could represent H initially, and another protecting groupbeing introduced in a later step) is used in a cyclocondensationreaction to make the imidazole ring. The conditions used will, ofcourse, depend on the X group chosen, and may include the intermediacyof the compound (VI). A review of imidazole-forming reactions may befound in Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984)vol. 5, pp. 457-498.

Preparation of compounds of formula (V) wherein both A and B arenitrogen atoms may proceed according to the route of Scheme 4.

A compound of formula (VII) may be available from commercial sources,particularly for K=chloride. Compounds bearing psuedohalide K groups maybe available from the corresponding dihydroxy compounds by treatmentwith an appropriate activating reagent, such as an organosulfonicanhydride or sulfonyl chloride. Compound (VII) may be converted to (V)by either (i) monoalkylation with a compound P—NH₂, followed byreduction of the nitro group; (ii) reduction of the nitro group, to givean amine compound of formula (VIII), followed by monoalkylation with acompound P—NH₂; or (iii) use of a source of ammonia (ammonia gas,ammonium hydroxide, etc.) in either route, followed by protection of theamine group with the group P. Pyrimidine chemistry of this type is wellrepresented in the literature, and is reviewed in ComprehensiveHeterocyclic Chemistry, vol. 6. Alkylation of chloropyrimidines withamine compounds can be accomplished under either acidic (e.g. HCl oracetic) or basic (trialkylamines, potassium tert-butoxide, etc.)conditions. Nitro groups in compounds of this type can be reduced toamino groups using one of any number of conditions, including catalytichydrogenation, tin dichloride, sodium dithionite, zinc metal, ironpowder, etc.

Preparation of compounds of formula (V) wherein either A or B representnitrogen atoms is shown in Scheme 5.

An hydroxypyridone compound of formula (IX) can be nitrated to givecompound (X) employing conditions such as concentrated or fuming nitricacid, optionally in the presence of concentrated sulfuric or aceticacid. The hydroxypyridone can be selectively monoactivated with a Kgroup to give a compound of formula (XI); one method to do this involvestreatment of the dicyclohexylamine salt of compound (X) with phosphorusoxychloride to give (XI) wherein K=Cl. Alternatively, both the hydroxyand pyridone groups in compound (X) can be activated at the same time,using stronger conditions such as phosphorus oxychloride and heat, orexcess toluenesulfonic anhydride, to give compound (XII). Compound (XI)may be converted to the protected amine compound (XIII) using the samegeneral route discussed above for the pyrimidines. Selectivemonoalkylation using compound (XII) is also possible, but will probablygive mixtures of regioisomeric products (XIV) and (XV). The nitro groupsin these compounds can then be reduced as discussed above, to givecompounds for formula (V) wherein either A or B is nitrogen.

An alternative approach to the method involving introduction of the R¹group at the initial step is shown in Scheme 6.

This is particularly useful in the cases where R¹ represents a groupwhere alkylation of compound (II) is impractical (e.g. a very bulky R¹group), but can also be used in a general manner. Here, compounds offormula (XVI) or (XVII) (either amino- or nitro-pyridines orpyrimidines) are alkylated with an amine reagent R¹—NH₂, under eitheracidic or basic conditions as described above. Nitro compound (XVIII)can be converted to amine compound (XIX) by nitro reduction reactionsdescribed earlier. Compound (XIX) can be cyclized to imidazole compound(XX). As above, this reaction will depend upon the choice of X group.For example, for X=CHR⁹, one can use an orthoester reagent such asR²CH(R⁹)C(OR)₃, with heating in neat solution or high-boiling solvents,and the optional presence of an acid catalyst (such as hydrochloric orsulfuric acid) (see Montgomery and Temple, J. Org. Chem. 1960, 25, 395).For X=NR¹⁰, the cyclization is performed using reagents such as anguanidine reagent of the structure R²R¹⁰N—C(═NH)NH₂ or a urea-derivedreagent of the structure R²R¹⁰N—C(═NH)D, where D represents a group likeOCH₃, SCH₃ or SO₂CH₃. For X=O, the ring is formed using a reagent of thestructure (R²O)₄C (with acetic acid catalysis), provided one has accessto the reagent with the R² group of choice (see Brown and Lynn, J. Chem.Soc. Perkin Trans. I 1974, 349). Alternatively, 10 the diamine (XIX) istreated with phosgene, followed by O-alkylation to introduce the R²group (such as a reagent like R²—I or R²—Br). A similar route can beused for X=S, which would use thiophosgene or some similar reagent,followed by S-alkylation with the R² group. The sulfur atom in thiscompound (and sulfide groups throughout the molecule in general) can beoxidized to either the sulfoxide or sulfone if desired by treatment withan appropriate oxidizing agent such as potassium permanganate, potassiumperoxomonosulfate or m-chloroperbenzoic acid. Finally, compound (XX) canbe 20 used in an aryl coupling reaction as described above to replacethe K group with the desired aryl group in compound (I).

Methods of synthesis of compounds R¹—OH, R¹—J and R¹—NH₂ are related, inthat the alcohol can be used in the synthesis of the other twocompounds, as is shown in Scheme 7.

For example, the hydroxy group may be converted to the following Jgroups, using the indicated reagents (this route is not limited to theseJ groups): methanesulfonate, using methanesulfonyl chloride or anhydrideand an appropriate base; toluenesulfonate, using toluenesulfonylchloride or anhydride and an appropriate base; iodide; usingiodine/triphenylphosphine; bromide, using phosphorus tribromide orcarbon tetrabromide/triphenylphosphine; or trifluoromethanesulfonate,using trifluoromethane-sulfonic anhydride and an appropriate base. Bothcompounds R¹—OH and R¹—J are used in the methods portrayed in Scheme 1.Conversion of R¹—J to R¹—N₃ requires the use of an azide source, such assodium azide, and a solvent such as dimethylsulfoxide ordimethylformamide, or water and a phase-transfer catalyst (such astetrabutylammonium hydrogen sulfate). Reduction of the azide compoundR¹—N₃ to R¹—NH₂ may be accomplished using reagents such as sodiumborohydride or triphenylphosphine, or hydrogen gas and a catalyst (suchas palladium on carbon). The amine R¹—NH₂ may then be employed in themethods portrayed in Scheme 6.

In the cases where the compound R¹—OH could be represented by astructure of formula (XXI) (Scheme 8), wherein R^(1a) and R^(1b)represents substructures which, taken together with the carbinol methinegroup, comprise the entire group R¹, this compound may be prepared byaddition to a carbonyl compound.

This route is particularly useful in the case where R^(1a) orR^(1b)represents a cycloalkyl group, such as cyclopropyl. Anorganometallic reagent (where M′ represents a metallic group, such asLi, CuCN, CuI, MgCl, MgBr, MgI, ZnCl, CrCl, etc.) can be allowed toreact with an aldehyde reagent to prepare the alcohol compound offormula (XXI). Alternatively, a ketone of formula (XXII) may be treatedwith a reducing agent, such as sodium borohydride, lithium aluminumhydride, etc., which will also generate the alcohol of formula (XXI).Standard methods of ketone synthesis may be used where appropriate inthe preparation of compounds for formula (XXII), which will be familiarto those skilled in the art of organic synthesis.

An homologous approach may also be employed in the synthesis of alcoholsR¹—OH, involving the ring-opening reaction of cyclic ether compoundswith organometallic reagents (Scheme 9).

Here, an organometallic reagent R^(1a)M′ is used, where M″ representsmetals such as Mg, Zn or Cu. Especially useful is the method describedin Huynh, et al., Tetrahedron Letters 1979, (17), pp. 1503-1506, whereorganomagnesium reagents are allowed to react with cyclic ethers withcatalysis provided by copper(I) iodide. Use of an epoxide compound offormula (XXIII) in this manner would result in synthesis of an alcoholcompound of formula (XXIV), and use of an oxetane compound of formula(XXV) would generate an alcohol of formula (XXVI). Both compounds (XXIV)and (XXVI) are variants of R¹—OH.

Synthesis of compound R¹—NH₂ with formula (XXVII) is portrayed in Scheme10.

A simple reductive amination of ketone (XXII) will produce amine(XXVII). This reaction may be performed using anhydrous ammonia in thepresence of hydrogen and a catalyst. Alternatively, addition of anorganometallic reagent to a nitrile compound gives and imine, which maybe treated in situ with a reducing agent (such as sodiumcyanoborohydride) to give amine (XXVII). Finally, a compound of formula(XXVIII), wherein Q is an optionally-substituted oxygen atom (i.e. anoxime) or nitrogen atom (i.e. a hydrazone), may be allowed to react withan organometallic reagent R^(1b)—M′″. Here, metallic groups M′″ such asMgBr, CuCl or CeCl₂ have been used in additions to oximes or hydrazones.The intermediate addition products of formula (XXIX) may be subjected toreductive cleavage (using conditions such as sodium/liquid ammonia orcatalytic hydrogenation), which will afford amines (XXVII).

Amino acids, either naturally-occurring or synthetic, are potentialsources of useful starting materials for the synthesis of the compoundsof this invention. Scheme 11 shows some possible applications of thisapproach.

Protected amino acids of formula (XXXI) are prepared from the parentcompounds of formula (XXX); useful protecting groups (“Prot”) includetert-butoxycarbonyl, benzyloxycarbonyl and triphenylmethyl. Standardtexts in peptide chemistry describe this protection. The carboxylic acidgroup may be reduced using reagents such as lithium borohydride, whichgives alcohol (XXXII). The hydroxy group may be converted to a leavinggroup “J” as described before. The compound of formula (XXXIII) may betreated with appropriate reagents to produce a wide variety offunctional groups included in the scope of this invention (compound(XXXIV)); displacement of J with cyanide (sodium cyanide in warmdimethylformamide may be used here) gives a nitrile, displacement of Jwith a mercaptan (in the presence of a base, such as potassiumcarbonate) gives a disulfide, displacement of J with a secondary aminegives a tertiary amine, etc.

The compounds of Formula (I) with unsaturated R¹ groups can be a furthersource of compounds covered under this invention. Unsaturated (doubleand triple) bonds can take part in cycloaddition chemistry withappropriate reagents (Scheme 12). Cycloaddition of an alkyne compound ofFormula XXXVI with 1,3-dienes to give six-membered ring compounds likethat of Formula XXXVII (commonly known as the Diels-Alder reaction), andcycloaddition with 3-atom dipolar reagents to give heterocycliccompounds of Formula XXXVIII, are familiar to those skilled in the artof organic synthesis. One specific example of this approach is thesynthesis of an isoxazole compounds of Formula XXXIX from the alkyneXXXVI and a nitrile oxide reagent.

The synthetic procedure in Scheme 13 shown below may be used to prepare4,5-c imidazopyridines.

Nitration of 2,4-dihydroxypyridine (XXXX) with HNO₃ as described earlier(Koagel et al. Recl. Trav. Chim. Pays-Bas. 29, 38, 67, 1948) gave thecorresponding 3-nitropyridone (XXXXI) which was treated with an organicamine base, such as cycloheptyl amine to give selectively thecorresponding 4-chloropyridone (XXXXIII). This in turn was reacted witha primary amine RNH₂, where R is a group described earlier in an aproticor protic solvent, such as CH₃CN, DMSO, DMF, or an alkyl alcohol in thepresence of an organic or inorganic base, such as a trialkylamine,K₂CO₃, Na₂CO₃ etc, and in temperature range of 20-200° C. to give the4-amino adduct (XXXXIII). Pyridone (XXXXIII) was converted to the2-chloropyridine (XXXXIV) by treatment with POCl₃, and (XXXXIV) wascoupled with an arylboronic acid ArB(OH)₂ under palladium catalysis togive (XXXXV). Nitropyridine (XXXXV) was reduced to the correspondingaminopyridine by use of Na₂S₂O₄ or a Fe, Sn or SnCl₂ and converted tothe imidazo[4,5-c]pyridine in refluxing propionic acid. The sametransformation can be affected by the use of a nitrile, an imidate,thioimidate or trialkylorthopropionate.

The synthetic procedure in Scheme 14 shown below may be used to prepare4,5-b imidazopyridines.

Reaction of 4-chloropyridone (XXXXII) with an aryl halide, such asbenzyl bromide in benzene and in the presence of Ag₂CO₃ as described inScheme 13 (Smith A. M.; et al. J. Med. Chem. 36, 8, 1993) and attemperature ranges of 30-80° C. afforded the corresponding2-benzyloxypyridine (XXXXVII). This was coupled with an arylboronicacid, ArB(OH)₂ under palladium-catalyzed conditions to give (XXXXIX).The benzyloxy group can be removed by treatment with a strong acid, suchas trifluoroacetic, triflic, sulfuric, HCl, etc. to give pyridone (L).This was converted to the 2-halopyridine with the action of POX₃, PX₅ orthe corresponding triflate, tosylate or mesylate, which was displacedwith a primary amine RNH₂ to give (LI). The nitro group was reducedunder conditions described in scheme 13 and the aminopyridine wascyclized to the imidazolo[4,5-b]pyridine (LII) under conditionsdescribed in scheme 13.

The following examples are provided to describe the invention in furtherdetail. These examples, which set forth the best mode presentlycontemplated for carrying out the invention, are intended to illustrateand not to limit the invention.

The methods discussed below in the preparation of8-ethyl-9-(1-ethylpentyl)-6-(2,4,6-trimethylphenyl)purine (Table 1,Example 2, Structure A) and9-butyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine (Table 1, Example 27,Structure A) may be used to prepare all of the examples of Structure Acontained in Table 1, Table 1A and Table 1B, with minor proceduralmodifications where necessary and use of reagents of the appropriatestructure.

The methods discussed below in the preparation of3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine(Table 1, Example 38, Structure B) and1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine(Table 1, Example 38, Structure C) may be used to prepare many of theexamples of Structures B and C contained in Table 1, Table 1A, Table 1Band Table 1C, with minor procedural modifications where necessary anduse of reagents of the appropriate structure.

EXAMPLE 2 Preparation of8-Ethyl-9-(1-ethylpentyl)-6-(2,4,6-trimethylphenyl)purine

Part A. A solution of 5-amino-4,6-dichloropyrimidine (10.0 g, 61.0 mmol)and triethylamine (12.8 mL, 91.5 mmol) in ethanol (100 mL) was treatedwith benzylamine (7.30 mL, 67.1 mmol), and heated to 50° C. overnight.The resulting mixture was cooled, and the resulting crystalline solidwas collected by filtration. The solid was triturated with hexane,refiltered and dried under vacuum. A second crop was collected from themother liquor and purified like the first crop to afford in total 12.67g (48.8 mmol, 80%) of 5-amino-6-benzylamino-4-chloropyrimidine. TLCR_(F) 0.10 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.62(1H, s), 7.13-6.97 (SH, m), 6.61 (1H, br t, J=5 Hz), 4.43 (2H, d, J=5.5Hz), 4.24 (2H, br s). MS (NH₃—CI): m/e 238 (4), 237 (33), 236 (15), 235(100).

Part B. A solution of the diamine from Part A (10.45 g, 44.5 mmol) and 3drops concentrated hydrochloric acid in triethyl orthopropionate (70 mL)was heated to 100° C. for 1 hour, then cooled, poured into water (200mL) and extracted with ethyl acetate (2×200 mL). The extracts werewashed in sequence with brine (100 mL), then combined, dried overanhydrous sodium sulfate, filtered and evaporated. The residue wasseparated by column chromatography (silica gel, 20:80 ethylacetate-hexane) to afford the product,N-(6-benzylamino-4-chloropyrimidin-5-yl)-O-ethyl-propionimidate (12.82g, 40.2 mmol, 90%) as a crystalline solid, m.p. 85-86° C. TLC R_(F) 0.25(20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.19 (1H, s),7.35-7.29 (5H, m), 5.21 (1H, br t, J=5 Hz), 4.70 (2H, d, J=5.9 Hz), 4.29(2H, br), 2.15 (2H, br q, J=7.3 Hz), 1.35 (3H, t, J=7.0 Hz), 1.06 (3H,t, J=7.3 Hz). MS (NH₃—CI): m/e 322 (6), 321 (34), 320 (20), 319 (100).

Part C. A solution of the imidate compound prepared in Part B above(10.66 g, 33.4 mmol) and p-toluenesulfonic acid monohydrate (100 mg) indiphenyl ether (10 mL) was heated to 170° C. for 2 hours. The resultingmixture was cooled and poured into 50 mL water. This was extracted withethyl acetate (2×50 mL), and the extracts were washed in sequence withbrine (50 mL), combined, dried over anhydrous sodium sulfate, filteredand evaporated. The residual material was separated by columnchromatography (silica gel, hexane to remove diphenyl ether, then 30:70ethyl acetate-hexane) to afford the product,9-benzyl-6-chloro-8-ethylpurine, as an oil (8.16 g, 29.9 mmol, 89%). TLCR_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.72(1H, s), 7.37-7.29 (3H, m), 7.19-7.14 (2H, m), 5.46 (2H, s), 2.89 (2H,q, J=7.7 Hz), 1.38 (3H, t, J=7.7 Hz). MS (NH₃—CI): m/e 276 (6), 275(36), 274 (20), 273 (100).

Part D. A solution of zinc chloride (5.32 g, 39.1 mmol) in anhydrous,freshly-distilled tetrahydrofuran (50 mL) was treated at ambienttemperature with a solution of mesitylmagnesium bromide (39.1 mL, 1.0 M,39.1 mmol) in diethyl ether. After 45 minutes, a separate flaskcontaining a solution of bis(triphenylphosphine)-palladium dichloride(0.92 g, 1.3 mmol) in tetrahydrofuran (30 mL) was treated with asolution of diisobutylaluminum hydride (2.6 mL, 1.0 M, 2.6 mmol) inhexane. This mixture was allowed to stir for 15 minutes, then treatedwith the mesitylzinc chloride solution dropwise by cannula. Then, thechloropurine compound in 10 mL tetrahydrofuran solution was added bysyringe, and the mixture was allowed to stir for 12 hours at ambienttemperature. It was poured into water (150 mL), and acidified withdropwise addition of 1 N aqueous hydrochloric acid until the mixture ishomogeneous. This is extracted with ethyl acetate (2×150 mL), and theextracts were washed in sequence with saturated brine solution (100 mL),combined, dried over anhydrous sodium sulfate, filtered and evaporated.The residue was separated by column chromatography (silica gel, 30:70ethyl acetate-hexane) to afford the product,9-benzyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine (6.68 g, 18.7 mmol,72%), as an off-white waxy solid, m.p. 121-122° C. ¹H NMR (300 MHz,CDCl₃): d 9.00 (1H, s), 7.38-7.31 (3H, m), 7.23-7.21 (2H, m), 6.96 (2H,s), 5.50 (2H, s), 2.84 (2H, q, J=7.6 Hz), 2.33 (3H, s), 2.06 (6H, s),1.26 (3H, t, J=7.5 Hz). MS (NH₃—CI): m/e 359 (3), 358 (26), 357 (100).

Part E. A solution of the benzyl compound from Part D above (5.33 g,14.95 mmol) in trifluoroacetic acid (320 mL) partitioned into four Parrbottles, and each was treated with 0.8 g 20% palladium hydroxide oncarbon. The bottles were each subjected to hydrogenation (50 psi) inshaker apparati for 18 hours. The atmospheres were purged with nitrogen,and the solutions were combined, filtered through celite and evaporated.The residual material was separated by column chromatography (silicagel, 50:50 ethyl acetate-hexane) to afford the product,8-ethyl-6-(2,4,6-trimethylphenyl)purine (3.75 g, 14.1 mmol, 94%), as awhite crystalline solid, m.p. 215-217° C. TLC R_(F) 0.17 (50:50 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 12.35 (1H, br s), 9.03 (1H,s), 6.96 (2H, s), 3.05 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.05 (6H, s),1.50 (3H, t, J=7.7 Hz). MS (NH₃—CI): m/e 269 (2), 268 (19), 267 (100).

Part F. A solution of the purine compound from Part E above (200 mg,0.75 mmol), 3-heptanol (0.13 mL, 0.90 mmol) and triphenylphosphine (0.24g, 0.90 mmol) in freshly-distilled tetrahydrofuran (5 mL) was cooled to0° C., and treated with diethyl azodicarboxylate (0.14 mL, 0.90 mmol)dropwise by syringe. The mixture was allowed to stir for 12 hours, thenevaporated. The residual material was separated by column chromatography(silica gel, 15:85 ethyl acetate-hexane) to, afford the title product asa white solid (0.152 g, 0.42 mmol, 56%), m.p. 99-100° C. TLC R_(F) 0.17(10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.91 (1H, s),6.95 (2H, s), 4.22 (1H, br), 2.92 (2H, q, J=7.7 Hz), 2.41 (2H, br), 2.32(3H, s), 2.10-1.98 (2H, m), 2.05 (3H, s), 2.04 (3H, s), 1.37 (3H, t,J=7.5 Hz), 1.34-1.23 (4H, m), 0.84 (3H, t, J=7.1 Hz), 0.81 (3H, t, J=7.5Hz). MS (NH₃—CI): m/e 367 (3), 366 (27), 365 (100).

EXAMPLE 27 Preparation of9-Butyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine

A solution of 8-ethyl-6-(2,4,6-trimethylphenyl)purine (200 mg, 0.75mmol) in anhydrous dimethylfomamide (5 mL) was cooled to 0° C., andtreated with sodium hydride dispersion in mineral oil (72 mg 50% w/w,1.50 mmol). After 1 hour, bromobutane (0.10 mL, 0.90 mmol) was added bysyringe, and the mixture was allowed to stir for 12 hours. It was pouredinto ethyl acetate (120 mL), and was washed with water (3×120 mL) andbrine (100 mL). The aqueous layers were back-extracted in sequence withethyl acetate (120 mL), and the extracts were combined, dried overanhydrous sodium sulfate, filtered and evaporated. The residue wasseparated by column chromatography (silica gel, 20:80 ethylacetate-hexane) to afford the title product as a viscous oil (64.2 mg,0.20 mmol, 27%). TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): d 8.96 (1H, s), 6.95 (2H, s), 4.25 (2H, t, J=7.5 Hz),2.93 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.04 (6H, s), 1.91-1.86 (2H, m),1.50-1.38 (2H, m), 1.39 (3H, t, J=7.7 Hz), 1.01 (3H, t, J=7.5 Hz). MS(NH₃—CI): m/e 325 (3), 324 (23), 323 (100).

EXAMPLE 35 Preparation of6-(2,4-Dichlorophenyl)-8-ethyl-9-(1-ethylpentyl)purine

A solution of 2,4-dichlorobenzeneboronic acid (572 mg, 3.00 mmol) andethylene glycol (205 mg, 3.30 mmol) in benzene (20 mL) was heated toreflux with azeotropic removal of water for a period of 8 h. Theresulting solution was cooled, and treated with6-chloro-8-ethyl-9-(1-ethylpentyl)purine (see Example 2, Part C above;562 mg, 2.00 mmol), thallium carbonate (1.03 g, 2.20 mmol) andtetrakis(triphenylphosphine)palladium (116 mg, 0.10 mmol). The resultingmixture was heated to reflux with stirring for 12 h, then cooled,filtered through celite and evaporated. The resulting residue wasseparated by column chromatography (silica gel, 10:90 ethylacetate-hexane) to afford the title compound as a viscous oil (530 mg,1.35 mmol, 68%). TLC R_(F) 0.31 (20:80 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): d 8.94 (1H, s), 7.71 (1H, d, J=8.4 Hz), 7.58 (1H, d,J=1.8 Hz), 7.41 (1H, dd, J=8.4, 1.8 Hz), 4.27 (1H, br), 2.95 (2H, q,J=7.3 Hz), 2.41 (2H, br), 2.11-1.98 (2H, br), 1.42 (3H, t, J=7.3 Hz),1.37-1.20 (3H, m), 1.09-0.99 (1H, m), 0.84 (3H, t, J=7.7 Hz), 0.82 (3H,t, J=7.7 Hz). MS (NH₃—CI): m/e calc'd for C₂₀H₂₅NCl₂: 391.1456, found391.1458; 395 (11), 394 (14), 393 (71), 392 (29), 391 (100).

EXAMPLE 38 Preparation of3-(1-Cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine

Part A. 2,4-Dihydroxypyridine (15.0 g, 135 mmol) was heated in HNO₃ (85mL) at 80° C. for 15-20 min at which time it went into solution. Thetemperature was maintained for 5 min and after cooling it was pouredinto ice/water (˜200 mL). The precipitated solid was collected and dried(19.0 g, 90% yield). ¹H NMR (300 MHz, dmso d6): 12.3-12.5 (1H, brs),11.75-11.95 (1H, brs), 7.41 (1H, d J=7.3 Hz), 5.99 (1H, d J=7.3 Hz).

Part B. 4-Hydroxy-3-nitropyridone (8.0 g, 51.25 mmol) and cycloheptylamine (6.8 mL, 53.4 mmol) were heated at reflux in methanol (100 mL) for15 min. The solvent was stripped off and the residual solid was washedwith 1:1 EWtOAc/hexanes and dried under vacuum. The cycloheptyl aminesalt was stirred in POCl₃ (60 mL) for 40 h and poured into ice/water(600 mL). The precipitated produced was collected and dried under vacuum(7.0 g, 78% yield). ¹H NMR (300 MHz, dmso d6): 12.8-13.05 (1H, brs),7.73 (1h, d J=7.0 Hz), 6.50 (1H, d J=7.0 Hz).

Part C. 4-Chloro-3-nitro-pyridone (0.5 g, 2.86 mmol) Ag₂CO₃ (0.83 g, 3mmol) and benzyl bromide (0.36 mL, 3 mmol) were stirred in dry benzene(20 mL) at 60° C. for 5 h. The reaction mixture was filtered andstripped in vacuo. The residue was chromatographed on silica gel (10%EtOAc/hexanes eluent) to give the product (0.6 g, 79%). ¹H NMR (300 MHz,CDCl₃): 8.15 (1H, d J=4.0 Hz), 7.30-7.42 (5 H, m), 7.04 (1H, d J=4.0Hz), 5.50 (2H, s).

Part D. 2-Benzyloxy-4-chloro-3-nitropyridine (0.5 g, 1.9 mmol),2,4-dichlorophenylboronic acid (0.363 g, 1.9 mmol) Pd(PPh₃)₂Cl₂ (76 mg,0.11 mmol) and Ba(OH)₂.8H₂O (0.6 g, 1.9 mmol) were heated at reflux in1,2-dimethoxyethane (6 mL), and water (6 mL) for 5 h. The mixture waspartitioned between EtOAc (100 mL) and water (30 mL) and the EtOAc waswashed with water, brine, dried and stripped in vacuo. The residue waschromatographed on silica gel (10% EtOAc/hexanes eluent) to give theproduct (370 mg, 52% yield). ¹H NMR (300 MHz, CDCl₃): 8.31 (1H, d J=5.1Hz), 7.51 (1H, d J=2.2 Hz), 7.30-7.43 (6H, m), 7.20 (1H, d J 8.0 Hz),6.91 (1H, d J=5.1 Hz), 5.56 (2h, s).

Part E. 2-Benzyloxy-4-(2,4-dichlorophenyl)-3-nitropyridine (1.65 g, 4.39mmol) was stirred in CF₃CO₂H(5 mL) at 25° C. for 4 h. The CF₃CO₂H wasstripped in vacuo and the residue was washed with 20% EtOAc/hexanes andused in the next reaction. ¹H NMR (300 MHz, CDCl₃): 7.62 (1H, d J=7.0Hz), 7.53 (1H, d J=2.2 Hz), 7.34 (1H, dd J=7.0, 2.2 Hz), 7.22 (1H, dJ=8.1 Hz), 6.33 (1H, d J=7.0 Hz).

Part F. 4-(2,4-dichlorophenyl)-3-nitropyridone (4.39 mmol) was heated atreflux in POCl₃ (5 mL) for 5 h. After cooling it was poured intoice/water (˜60 mL) and extracted with EtOAc (2×100 mL). The EtOAc waswashed with sat NaHCO₃, brine, dried and stripped in vacuo. Used in thenext reaction without further purification. ¹H NMR (300 MHz, CDCl₃):8.60 (1H, d J=5.2 Hz), 7.54 (1H, d, J=2.2 Hz), 7.36 (1H, dd J=8.1, 2.2Hz), 7.20 (1H, d J=8.1 Hz).

Part C. 2-Chloro-4-(2,4-dichlorophenyl)-3-nitropyridine (0.5 g, 1.65mmol) 1-cyclopropylpropylamine hydrochloride (461 mg, 3.4 mmol) anddiisopropyl ethylamine (1.26 mL, 0.72 mmol) were heated at reflux inCH₃CN (10 mL) for 64 h. The mixture was partitioned between EtOAc (70mL) and water (40 mL). The aqueous layer was extracted with EtOAc (50mL) and the combined EtOAc exctracts washed with brine, dried andstripped in vacuo. The residue was chromatographed on silica gel (10%EtOAc/hexanes eluent) to give the product (310 mg, 51% yield). ¹H NMR(300 MHz, CDCl₃): 8.29 (1H, d J=4.7 Hz), 7.76 (1H, brd J=8.0 Hz), 7.46(1H, d J=2.2 Hz), 7.32 (1H, dd J=8.5, 2.2 Hz), 7.15 (1H, d J=8.5 Hz),3.72-3.85 (1H, m)), 1.70-1.80 (2H, m), 0.90-1.08 (4H, m), 0.30-0.66 (4H,m).

Part H.2-(1-cyclopropyl)propylamino-4-(2,4-dichlorophenyl)-3-nitropyridine (310mg, 0.85 mmol) was dissolved in dioxane (8 mL) and water (8 mL)containing conc NH₄OH (0.3 mL) was added, followed by Na₂S₂O₄ (1.1 g,6.86 mmol). The reaction was stirred at 25° C. for 4 h and extractedwith EtOAc (100 mL) The EtOAc was washed with brine, dried and strippedin vacuo. The residue was chromatographed on silica gel (25%EtOAc/hexanes and 1% conc NH₄OH eluent) to give the product (150 mg, 53%yield). ¹H NMR (300 MHz, CDCl₃): 7.73 (1H, d J=5.5 Hz), 7.53 (1H, dJ=1.8 Hz), 7.35 (1H, dd J=8.1, 1.8 Hz), 7.24 (1H, d J=8.1 Hz), 6.35 (1H,d J=5.5 Hz), 4.3 (1H, brs), 3.5 (1H, brs), 3.42-3.55 (1H, m), 3.04 (2H,brs), 1.70-1.81 (2H, m), 0.88-1.08 (4H, m), 0.3-0.6 (4H, m).

Part I.3-amino-2-(1-cyclopropyl)propylamino-4-(2,4-dichlorophenyl)-pyridine(140 mg, 0.42 mmol) was heated at reflux in propionic acid (5 mL) for 23h. Then the mixture was diluted with water (50 mL), neutralized withsolid NaHCO₃ and basified with 50%NaOH. Then it was extracted with EtOAc(80 mL) and the EtOAc was dried and stripped in vacuo. The residue waschromatographed on silica gel (10% and 20%EtOAc/hexanes eluant) to givethe product, which was crystallized from hexanes (70 mg, 45% yield) mp118-119° C. ¹H NMR (300 MHz, CDCl₃): 8.31 (1H, d J=4.7 Hz), 7.62 (1H, dJ=7.2 Hz), 7.55 (1H, d J=1.8 Hz), 7.37 (1H, dd J=7.2, 1.8 Hz), 7.23 (1H,d J=4.7 Hz), 3.50-3.70 (1H, brs), 2.87-2.96 (2H, q), 2.36-2.56(1H, m),2.18-2.35 (1H, m), 1.90-2.05 (1H, m), 1.38 (3H, t), 0.86 (3H, t),0.75-0.84 (1H, m), 0.40-0.54 (1H, m), 0.15-0.25 (1H, m).

EXAMPLE 38A Preparation of1-(1-Cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine

Part A. A mixture of 4-chloro-3-nitro-2-pyridone (2.0 g, 11.4 mmol),1-cyclopropylpropyl amine hydrochloride (1.5 g, 11.4 mmol) andN,N-diisopropylethylamine (4.8 ml, 27.4 mmol) in CH₃CN (50 ml) werestirred at 25° C. for 16 h and at reflux for 4 h. After cooling it wasstripped in vacuo, and the residue was partitioned between EtOAc (100mL) and H₂O (50 mL). The insolubles were separated, washed with H₂O andEtOAc and vacuum dried 1.51 g. The filtrate layers were separated andthe aqueous layer was extracted with EtOAc (2×50 mL). The Combinedextracts were washed with brine, dried over MgSO₄, filtered and concd.in vacuo. The residue was washed with EtOAc (2×) and vacuum dried, togive 0.69 g; yellow solid. Combined wt. of4-(1-cyclopropylpropyl)amino-3-nitro-2-pyridone 2.20 g, 81% yield. ¹HNMR (300 MHz, dmso d6): 11.19 (1H, br), 8.94 (1H, d J=8.8 Hz), 7.33 (1H,t J=6.9 Hz), 6.03 (1H, d J=7.7 Hz), 3.18-3.24 (1H, m)r, 1.60-1.74 (2H,m), 1.03-1.11(1H, m), 0.91 (3H, t), 0.40-0.60 (1H, m), 0.20-0.39 (1H,m).

Part B. 4-(1-Cyclopropyl)propylamino-3-nitro-2-pyridone (2.20 g, 9.27mmol) was stirring in POCl₃ (15 mL) at 25° C. for 16 h. Then it waspoured into ice/water (220 mL) and stirred until all the POCl₃ hadreacted. The mixture was neutralized with solid NaHCO₃, filtered andextracted with EtOAc (3×60 mL). The combined organic extracts werewashed with brine, dried over MgSO₄, filtered and stripped in vacuo. Thecrude oil was chromatographed on silica gel (100 g.) and eluted with agradient from 10-20% EtOAc/hexane to afford 1.91 g2-chloro-4-(1-cyclopropylpropyl)amino-3-nitropyridine, 81% yield. ¹H NMR(300 MHz, CDCl₃): 7.96 (1H, d J=6.3 Hz), 6.58 (1H, d J=6.3 Hz), 6.52(1H, brd J=5.5 Hz), 2.90-3.00 (1H, m), 1.61-1.82 (2H, m), 1.01 (3H, tJ=7.7 Hz), 0.90-1.02 (1H, m), 0.51-0.70 (2H, m), 0.21-0.34 (2H, m).

Part C. In a dried flask, under N₂, a mixture of2-chloro-4-(1-cyclopropyl)propylamino-3-nitropyridine (730 mg, 2.85mmol), 2,4-dichlorophenylboronic acid (544 mg, 2.85 mmol),dichlorobis(triphenylphosphine)palladium(III) (114 mg, 0.17 mmol) andbarium hydroxide octahydrate (899 mg, 2.85 mmol) was heated at reflux indimethoxyethane (8.6 mL) and H₂O (8.6 mL for 1.5 h. After cooling it waspartitioned between EtOAc (100 mL) and water (20 mL) and filteredthrough celite. The aqueous layer was extracted with EtOAc (2×50 mL).The combined organics were washed with brine, dried over MgSO₄, filteredand stripped in vacuo. The residue was chromatographed on silica gel (40gm), and eluted with 30% EtOAc/hexane to afford a yellow oil, 1.00 g,90% yield. ¹H NMR (300 MHz, CDCl₃): 8.24 (1H, d J=6.2 Hz), 7.87 (1H, brdJ=7.3 Hz), 7.43 (1H, s), 7.34 (2H, s), 6.71 (1H, d J=6.2 Hz), 3.00-3.10(1H, m), 1.70-1.85 (2H, m), 0.95-1.15 (4H, m), 0.50-0.71 (2H, m),0.25-0.40 (2H, m).

Part D. The product from Part C (0.94 g, 2.57 mmol), by dissolving indioxane (26 ml), H₂O (26 ml) and conc. NH₄OH (1.0 ml) while addingNa₂S₂O₄ and stirring at room temperature for 2 hrs. Added CH₂Cl₂ andextracted. Extracted the aqueous layer with CH₂Cl₂ (2×). Combined theorganics and washed with brine, dried over MgSO₄, filtered and concd. invacuo to give a yellow solid, 1.01 g. It was carried over to the nextreaction without purification.

Part E. The amine from Part D (1.01 g, 3.00 mmol) was cyclized byrefluxing with propionic acid (27 ml, 365.45 mmol) for 8 hrs. Allowed tocool to RT. then basified with 1M NaOH and 50% NaOH. Extracted withEtOAc (2×60 mL) and CH₂Cl₂(60 mL). Combined the organics and washed withH₂O, brine, dried over MgSO₄, filtered and concd. in vacuo. The crudeoil was chromatographed on silica gel (40 g.) and eluted with 30%EtOAc/hexane to obtain a pale yellow solid (triturated from hexane), 520mg, 46% yield. H NMR (300 MHz, CDCl₃): 8.43 (1H, d J=5.8 Hz), 7.63 (1H,d J=8.1 Hz), 7.55 (1H, d J=1.8 Hz), 7.46 (1H, d J=5.8 Hz), 7.36 (1H, ddJ=8.1 , 1.8 Hz), 3.40-3.50 (1H, m), 2.80-2.90 (2H, q J=7.7 Hz),2.10-2.30 (2H, m), 1.50-1.64 (1H, m), 1.37 (3H, t J=7.3 Hz), 0.87 (3H, tJ=7.3 Hz), 0.81-0.91 (1H, m), 0.48-0.58 (2H, m), 0.18-0.26 (1H, m).Elemental analysis calcd for C₂₀H₂₁N₃Cl₂: C, 64.18; H, 5.665; N, 11.23;found: C, 64.37; H, 5.66; N, 11.15.

EXAMPLE 831 Preparation of6-(2-Chloro-4-methoxyphenyl)-9-dicyclopropylmethyl-8-ethylpurine

Part A. A solution of dicyclopropyl ketone (50 g) in absolute methanol(150 mL) in an autoclave vessel was charged with W4 Raney nickel (12 g,washed free of water and in methanol slurry) and then anhydrous ammonia(17 g). The mixture was subjected to 120 atm of hydrogen at 150-160° C.for 5 hours, then cooled and excess gasses purged. The resulting slurrywas filtered through celite, and the filtrate was distilled to aboutone-third the original volume (atmospheric pressure, Vigreaux column).The pot solution was cooled to 0° C., diluted with 3 volumes diethylether, and treated with 4 N hydrochloric acid solution in anhydrousdioxane until precipitate formation ceased. The solid product(dicyclopropylmethylamine hydrochloride) was collected by filtration,washed with excess diethyl ether, and dried under vacuum (45.22 g, 306mmol, 67%). ¹H NMR (300 MHz, methanol-d₄): d 1.94 (1H, t, J=9.3 Hz),1.11-0.99 (2H, m), 0.75-0.59 (4H, m), 0.48-0.37 (4H, m). MS (NH₃-DCI):m/e 114 (5), 113 (100).

Part B. A solution of 5-amino-4,6-dichloropyrimidine (5.00 g, 30.5 mmol)and diisopropylethylamine (12.0 mL, 68.9 mmol) in ethanol (100 mL) wastreated with the amine from Part A (3.81 g, 25.8 mmol), and heated toreflux for 72 h. The resulting mixture was cooled and poured into water(300 mL), which was extracted with ethyl acetate (2×300 mL). Theextracts were washed with brine, combined, dried over sodium sulfate,filtered and evaporated. The residual oil was separated by columnchromatography (30:70 ethyl acetate-hexane), and the desired product,5-amino-4-chloro-6-dicyclopropylmethylaminopyrimidine, was trituratedwith warm ether-hexane, collected by filtration, and dried under vacuum(3.15 g, 13.2 mmol, 43%). m.p. 137-138° C. TLC R_(F) 0.17 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.01 (1H, s), 4.95 (1H, brd, J=7.3 Hz), 3.45 (1H, q, J=7.0 Hz), 3.37 (2H, br s), 1.06-0.94 (2H,m), 0.59-0.32 (8H, m). MS (NH₃—CI): m/e 243 (1), 242 (5), 241 (36), 240(16), 239 (100).

Part C. A solution of the diamine from Part B (1.80 g, 7.54 mmol) and 1drop concentrated hydrochloric acid in triethyl orthopropionate (12 mL)was heated to 100° C. for 6 hours. The excess orthoester was removed bydistillation (partial vacuum, short-path), and the pot residuesolidified to give the product,N-(4-chloro-6-dicyclopropylmethylaminopyrimidin-5-yl)-O-ethyl-propionimidate.¹H NMR (300 MHz, CDCl₃): d 8.08 (1H, s), 4.84 (1H, br d, J=8.0 Hz), 4.35(2H, br), 3.45 (1H, q, J=7.7 Hz), 2.14 (2H, q, J=7.3 Hz), 1.41 (3H, t,J=7.1 Hz), 1.08 (3H, t, J=7.7 Hz), 1.03-0.93 (2H, m), 0.58-0.27 (8H, m).MS (NH₃—CI): m/e 327 (1), 326 (7); 325 (36), 324 (21), 323 (100).

Part D. A solution of the imidate compound prepared in Part C above andp-toluenesulfonic acid monohydrate (50 mg) in diphenyl ether (10 mL) washeated to 170° C. for 2 hours. The resulting mixture was cooled andseparated by column chromatography (silica gel, hexane to removediphenyl ether, then 30:70 ethyl acetate-hexane) to afford the product,6-chloro-9-dicyclopropylmethyl-8-ethylpurine, as an solid (1.42 g, 5.13mmol, 68% for both steps C and D). m.p. 99-100° C. TLC R_(F) 0.26 (30:70ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.63 (1H, s), 2.99(2H, br), 1.92 (1H, br), 1.50 (3H, t, J=7.3 Hz), 0.87-0.78 (2H, m),0.50-0.39 (4H, m), 0.20-0.10 (4H, m). MS (NH₃—CI): m/e 280 (6), 279(36), 278 (19), 277 (100).

Part E. A solution of 4-amino-3-chlorophenol hydrochloride (18.6 g, 103mmol) and sodium acetate (18.6 g, 227 mmol) in glacial acetic acid (200mL) was heated to gentle reflux for 12 hours, then cooled and pouredinto 4 volumes water. This was neutralized with portion wise addition ofsodium bicarbonate, and the resulting mixture was extracted with ethylacetate (2×500 mL). The extracts were washed with brine, combined, driedover magnesium sulfate, filtered and evaporated. The resulting solid wastriturated with warm ether; filtration and vacuum drying gave4-acetamido-3-chlorophenol (16.1 g, 86.7 mmol, 84%). m.p. 128-129° C.TLC R_(F) 0.14 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, 4:1CDCl₃.CD₃OD): d 7.66 (1H, d, J=8.8 Hz), 6.88 (1H, d, J=1.7 Hz), 6.74(1H, dd, J=8.8, 1.7 Hz), 2.19 (3H, s). MS (H₂O-GC/MS): m/e 186 (100).

Part F. A solution of the phenol of Part E (14.6 g, 78.8 mmol), methyliodide (10.0 mL, 160 mmol), and sodium carbonate (10.0 g, 94.3 mmol) inacetonitrile (200 mL) was heated to reflux for 48 hours, the cooled andpoured into water (800 mL). This was extracted with ethyl acetate (2×800mL), and the extracts were washed with brine, combined, dried overmagnesium sulfate, filtered and evaporated. The resulting solid wasrecrystallized from ether-ethyl acetate to afford pure product,2-chloro-4-methoxyacetanilide (13.2 g, 66.3 mmol, 84%), m.p. 118-119° C.(ether-ethyl acetate). TLC R_(F) 0.30 (50:50 ethyl acetate-hexane). ¹HNMR (300 MHz, CDCl₃): d 8.15 (1H, d, J=9.2 Hz), 7.39 (1H, br s), 6.92(1H, d, J 3.0 Hz), 6.82 (1H, dd, J=9.2, 3.0 Hz), 3.78 (3H, s), 2.22 (3H,s). MS (NH₃—CI): m/e 219 (19), 217 (60), 202 (40), 201 (14), 200 (100).

Part G. A solution of the amide from Part F (10.1 g, 50.7 mmol) andsodium hydroxide (10 mL, 5 N, 50 mmol) in 95% ethanol (200 mL) washeated to 50° C. for 24 hours. Then, an additional 5 mL sodium hydroxidesolution was added, and the mixture was heated to full reflux for anadditional 48 hours. The solution was cooled and evaporated, and theresidual material was partitioned between ether and water. The aqueousphase was extracted a second time with ether, and the-extracts werewashed with brine, combined, dried over sodium sulfate, filtered andevaporated. The resulting product, 2-chloro-4-methoxyaniline, waspurified by elution through a short column of silica gel with 30:70ethyl acetate-hexane, and the eluant was evaporated (7.98 g, 100%).

Part H. A solution of the aniline from Part G (7.98 g, 50 mmol) in conc.HCl (25 mL) was cooled to −5° C., and treated dropwise with aconcentrated aqueous solution of sodium nitrite (3.80 g, 55.1 mmol).After 30 minutes, the mixture was charged with 15 mL cyclohexane and 15mL dichloromethane, then treated dropwise with a concentrated aqueoussolution of potassium iodide (16.6 g, 100 mmol). This mixture wasallowed to stir for 4 hours, then was extracted with dichloromethane(2×100 mL). The extracts were washed in sequence with 1 N aqueous sodiumbisulfite (100 mL) and brine (60 mL), then combined, dried overmagnesium sulfate, filtered and evaporated to afford sufficiently pureproduct, 3-chloro-4-iodoanisole (7.00 g, 26.1 mmol, 52%). TLC R_(F) 0.39(5:95 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.69 (1H, d,J=8.8 Hz), 7.03 (1H, d, J=3.0 Hz), 6.57 (1H, dd, J=8.8, 3.0 Hz), 3.78(3H, s). MS (H₂O-GC/MS): m/e 269 (100).

Part I. A solution of the iodide compound from Part H(7.00 g, 26.1 mmol)in anhydrous tetrahydrofuran (50 mL) was cooled to −90° C., and treatedwith a hexane solution of n-butyllithium (16.5 mL, 1.6 M, 26.4 mmol).After 15 minutes, the solution was treated with triisopropylborate (6.10mL, 26.4 mmol) and was allowed to warm to ambient temperature over 6hours. The resulting mixture was treated with 6 N aqueous HCl (5 mL) andwater (5 mL), which was stirred for 1 hour, then poured into water (100mL) and extracted with ethyl acetate (2×100 mL). The extracts werewashed in sequence with 1 N aqueous sodium bisulfite and brine (80 mLeach), combined, dried over sodium sulfate, filtered and evaporated. Theresidual solid was triturated with 1:1 ether-hexane, collected byfiltration and dried under vacuum to afford pure product,2-chloro-4-methoxybenzeneboronic acid (3.05 g, 16.4 mmol, 63%). m.p.191-195° C.

Part J. A solution of the chloride from Part D (770 mg, 2.78 mmol), theboronic acid from Part I (770 mg, 4.13 mmol), 2 N aqueous sodiumcarbonate solution (4 mL, 8 mmol) and triphenylphosphine (164 mg, 0.625mmol) in DME (20 mL) was degassed by repeated cycles of brief vacuumpumping followed by nitrogen purging. To this was added palladium(II)acetate (35 mg, 0.156 mmol), and the mixture was degassed again and thenheated to reflux for 14 hours. It was cooled, and poured into water (100mL). This mixture was extracted with ethyl acetate (2×100 mL), and theextracts were washed in sequence with brine (60 mL), combined, driedover sodium sulfate, filtered and evaporated. The residual material wasseparated by column chromatography (silica gel, 15:85 ethylacetate-hexane) to afford the title product as a solid. This wasrecrystallized to purity from hexane (791 mg, 2.07 mmol, 74%). m.p.139-140° C. (hexane). TLC R_(F) 0.18 (30:70 ethyl acetate-hexane). ¹HNMR (300 MHz, CDCl₃): d 8.93 (1H, s), 7.74 (1H, d, J=8.4, Hz), 7.10 (1H,d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 4.20 (1H, v br), 3.87 (3H,s), 2.97 (2H, v br), 2.00 (2H, v br), 1.44 (3H, br t, J=7 Hz), 0.89-0.79(2H, m), 0.62-0.52 (2H, m), 0.51-0.40 (2H, m), 0.26-0.16 (2H, m). MS(NH₃—CI): m/e 387 (1), 386 (9), 385 (41), 384 (30), 383 (100). Analysiscalc'd for C₂₁H₂₃ClN₄O: C, 65.87; H, 6.05; N, 14.63; found: C, 65.77; H,6.03; N, 14.57.

In Table 1, Table 1A and Table 1B, melting point data correspond tocompounds of Structure A unless otherwise indicated.

TABLE 1

(A) (B) (C) Ex. mp. No. R² X R³ R⁴ R⁵ R¹¹ R⁶ R^(1a) R^(1b) ° C.^(a) 1CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ 128-129 2 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅C₄H₉  99-100 3 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ oil 4 CH₃ CH₂ H CH₃CH₃ H CH₃ C₂H₅ C₆H₅ — 5 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ 143-145 6CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 7 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇68-71 8 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ oil 9 CH₃ CH₂ H CH₃ CH₃H CH₃ C₂H₅ (CH₂)₂OH 196-197 10 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅(CH₂)₂—(Q1)^(b) oil 11 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(b) oil12 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 13 CH₃ CH₂ H CH₃ CH₃ H CH₃c-C₃H₅ C₄H₉ 120-121 14 CH₃ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ (CH₂)₂OH 209-21015 CH₃ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ H 140-150 16 CH₃ CH₂ H CH₃ CH₃ H CH₃c-C₃H₅ c-C₃H₅ 186-187 17 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ 121-122 18 CH₃CH₂ H CH₃ CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ oil 19 CH₃ CH₂ H CH₃ CH₃ H CH₃ H2-Br—C₆H₄ 84-85 20 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ 48-50 21 CH₃ CH₂H CH₃ CH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 22 CH₃ CH₂ H CH₃ CH₃ H CH₃ H2-(C₄H₉)—C₄H₉ — 23 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 24 CH₃ CH₂H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 25 CH₃ CH₂ H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 26CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₂H₅ 120-123 27 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₃H₇oil 28 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₄H₉ oil 29 CH₃ CH₂ H CH₃ CH₃ H CH₃CH₂OCH₃ CH₂OCH₃ — 30 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ OC₂H₅ 91-93 31 CH₃ CH₂H CH₃ CH₃ H CH₃ H (CH₃)₂CH 120-121 32 CH₃ CH₂ H CH₃ CH H CH₃ HO(CH₂)₂—CCH₃ — 33 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ — 34 CH₃ CH₂ H ClCl H H C₂H₅ C₂H₅ oil 35 CH₃ CH₂ H Cl Cl H H C₂H₅ C₄H₉ oil 36 CH₃ CH₂ HCl Cl H H C₂H₅ CH₂OCH₃ — 37 CH₃ CH₂ H Cl Cl H H C₂H₅ C₆H₅ — 38 CH₃ CH₂ HCl Cl H H C₂H₅ c-C₃H₅ oil (A) 118-119 (B) 125-126 (C) 39 CH₃ CH₂ H Cl ClH H C₂H₅ C₆H₁₃ — 40 CH₃ CH₂ H Cl Cl H H C₂H₅ C₃H₇ oil 41 CH₃ CH₂ H Cl ClH H C₂H₅ (CH₂)₂OCH₃ — 42 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂CN — 43 CH₃ CH₂ HCl Cl H H C₂H₅ (CH₂)₂—(Q1)^(b) — 44 CH₃ CH₂ H Cl Cl H H C₂H₅(CH₂)₂—(Q2)^(c) — 45 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 46 CH₃ CH₂ HCl Cl H H c-C₃H₅ C₄H₉ — 47 CH₃ CH₂ H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 48 CH₃CH₂ H Cl Cl H H c-C₃H₅ C₆H₅ oil 49 CH₃ CH₂ H Cl Cl H H c-C₃H₅ c-C₃H₅156-157 50 CH₃ CH₂ H Cl Cl H H H C₆H₅ oil 51 CH₃ CH₂ H Cl Cl H H H3-(CH₃O)—C₆H₄ oil 52 CH₃ CH₂ H Cl Cl H H H 2-Br—C₆H₄ — 53 CH₃ CH₂ H ClCl H H H 4-CH₃—C₆H₄ 114-115 54 CH₃ CH₂ H Cl Cl H H H 4-C₆H₅—C₆H₄ oil 55CH₃ CH₂ H Cl Cl H H H 2-(C₄H₉)-C₄H₉ — 56 CH₃ CH₂ H Cl Cl H H H3-(C₄H₉)-C₅H₁₀ — 57 CH₃ CH₂ H Cl Cl H H H (CH₂)₂OCH₃ — 58 CH₃ CH₂ H ClCl H H H CH₂OCH₃ — 59 CH₃ CH₂ H Cl Cl H H H C₂H₅ — 60 CH₃ CH₂ H Cl Cl HH H C₃H₇ — 61 CH₃ CH₂ H Cl Cl H H H C₄H₉ — 62 CH₃ CH₂ H Cl Cl H HCH₂OCH₃ CH₂OCH₃ — 63 CH₃ CH₂ H Cl Cl H H C₂H₅ OC₂H₅ — 64 CH₃ CH₂ H Cl ClH H H OC₂H₅ — 65 CH₃ CH₂ H Cl Cl H H H O(CH₂)₂—OCH₃ — 66 CH₃ CH₂ H Cl ClH H CH₂OCH₃ C₆H₅ — 67 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 68 CH₃ CH₂ HCH₃ OCH₃ H CH₃ C₂H₅ C₄H₉ oil 69 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ —70 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 71 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅c-C₃H₅ — 72 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 73 CH₃ CH₂ H CH₃ OCH₃H CH₃ C₂H₅ C₃H₇ — 74 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 75 CH₃CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 76 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅(CH₂)₂—(Q1)^(b) — 77 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 78CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 79 CH₃ CH₂ H CH₃ OCH₃ H CH₃c-C₃H₅ C₄H₉ — 80 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 81 CH₃ CH₂ HCH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ — 82 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅167-169 83 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H C₆H₅ 134-135 84 CH₃ CH₂ H CH₃ OCH₃H CH₃ H 3-(CH₃O)—C₆H₄ — 85 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 86 CH₃CH₂ H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 87 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H4-C₆H₅—C₆H₄ — 88 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 89 CH₃ CH₂ HCH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 90 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H(CH₃)₂OCH₃ — 91 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H CH₂OCH₃ — 92 CH₃ CH₂ H CH₃OCH₃ H CH₃ H C₂H₅ — 93 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H C₃H₇ — 94 CH₃ CH₂ HCH₃ OCH₃ H CH₃ H C₄H₉ — 95 CH₃ CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 96CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 97 CH₃ CH₂ H CH₃ OCH₃ H CH₃ HOC₂H₅ — 98 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 99 CH₃ CH₂ H CH₃OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 100 CH₃ CH₂ H CH₃ CH₃ H CH₃ H CH₃ 138-140 101H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ 198-199 102 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅C₄H₉ 147-148 103 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ 140-142 104 H CH₂ HCH₃ CH₃ H CH₃ C₂H₅ C₆H₅ — 105 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 106 HCH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 107 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ —108 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 109 H CH₂ H CH₃ CH₃ H CH₃C₂H₅ CH₂CN — 110 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 111 H CH₂H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 112 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅CH₂N(CH₃)₂ — 113 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 114 H CH₂ H CH₃ CH₃H CH₃ c-C₃H₅ CH₂OCH₃ — 115 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 116 H CH₂H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 117 H CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ — 118 HCH₂ H CH₃ CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 119 H CH₂ H CH₃ CH₃ H CH₃ H2-Br—C₆H₄ — 120 H CH₂ H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ — 121 H CH₂ H CH₃ CH₃H CH₃ H 4-C₆H₅—C₆H₄ — 122 H CH₂ H CH₃ CH₃ H CH₃ H 3-C₇H₁₅ oil 123 H CH₂H CH₃ CH₃ H CH₃ H 2-(C₂H₅)—C₆H₁₂ oil 124 H CH₂ H CH₃ CH₃ H CH₃ H(CH₂)₂OCH₃ — 125 H CH₂ H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 126 H CH₂ H CH₃ CH₃ HCH₃ H C₂H₅ — 127 H CH₂ Y CH₃ CH₃ H CH₃ H C₃H₇ — 128 H CH₂ H CH₃ CH₃ HCH₃ H C₄H₉ — 129 H CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 130 H CH₂ H CH₃CH₃ H CH₃ C₂H₅ OC₂H₅ — 131 H CH₂ H CH₃ CH₃ H CH₃ H OC₂H₅ — 132 H CH₂ HCH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 133 H CH₃ H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ —134 H CH₂ H Cl Cl H H C₂H₅ C₂H₅ — 135 H CH₂ H Cl Cl H H C₂H₅ C₄H₉ — 136H CH₂ H Cl Cl H H C₂H₅ CH₂OCH₃ — 137 H CH₂ H Cl Cl H H C₂H₅ C₆H₅ — 138 HCH₂ H Cl Cl H H C₂H₅ c-C₃H₅ — 139 H CH₂ H Cl Cl H H C₂H₅ C₆H₁₃ — 140 HCH₂ H Cl Cl H H C₂H₅ C₃H₇ — 141 H CH₂ H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 142H CH₂ H Cl Cl H H C₂H₅ CH₂CN — 143 H CH₂ H Cl Cl H H C₂H₅(CH₂)₂—(Q1)^(b) — 144 H CH₂ H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 145 H CH₂H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 146 H CH₂ H Cl Cl H H c-C₃H₅ C₄H₉ — 147 HCH₂ H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 148 H CH₂ H Cl Cl H H c-C₃H₅ C₆H₅ — 149H CH₂ H Cl Cl H H c-C₃H₅ c-C₃H₅ — 150 H CH₂ H Cl Cl H H H C₆H₅ — 151 HCH₂ H Cl Cl H H H 3-(CH₃O)—C₆H₄ — 152 H CH₂ H Cl Cl H H H 2-Br—C₆H₄ —153 H CH₂ H Cl Cl H H H 4-CH₃—C₆H₄ — 154 H CH₂ H Cl Cl H H H 4-C₆H₅—C₄H₄— 155 H CH₂ H Cl Cl H H H 2-(C₄H₉)—C₄H₉ — 156 H CH₂ H Cl Cl H H H3-(C₄H₉)—C₅H₁₀ — 157 H CH₂ H Cl Cl H H H (CH₂)₂OCH₃ — 158 H CH₂ H Cl ClH H H CH₂OCH₃ — 159 H CH₂ H Cl Cl H H H C₂H₅ — 160 H CH₂ H Cl Cl H H HC₃H₇ — 161 H CH₂ H Cl Cl H H H C₄H₉ — 162 H CH₂ H Cl Cl H H CH₂OCH₃CH₂OCH₃ — 163 H CH₂ H Cl Cl H H C₂H₅ OC₂H₅ — 164 H CH₂ H Cl Cl H H HOC₂H₅ — 165 H CH₂ H Cl Cl H H H O(CH₂)₂—OCH₃ — 166 H CH₂ H Cl Cl H HCH₂OCH₃ C₆H₅ — 167 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 168 H CH₂ H CH₃OCH₃ H CH₃ C₂H₅ C₄H₉ — 169 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 170 HCH₂ H CH₃ OCH₂ H CH₃ C₂H₅ C₆H₅ — 171 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅— 172 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 173 H CH₂ H CH₃ OCH₃ H CH₃C₂H₅ C₃H₇ — 174 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 175 H CH₂ H CH₃OCH₃ H CH₃ C₂H₅ CH₂CN — 176 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b)— 177 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 178 H CH₂ H CH₃ OCH₃H CH₃ C₂H₅ CH₂N(CH₃)₂ — 179 H CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 180 HCH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 181 H CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅C₆H₅ — 182 H CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 183 H CH₂ H CH₃ OCH₃ HCH₃ H C₆H₅ — 184 H CH₂ H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 185 H CH₂ HCH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 186 H CH₂ H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ —187 H CH₂ H CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 188 H CH₂ H CH₃ OCH₃ H CH₃ H2-(C₄H₉)—C₄H₉ — 189 H CH₂ H CH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 190 H CH₂H CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 191 H CH₂ H CH₃ OCH₃ H CH₃ H CH₂OCH₃ —192 H CH₂ H CH₃ OCH₃ H CH₃ H C₂H₅ — 193 H CH₂ H CH₃ OCH₃ H CH₃ H C₃H₇ —194 H CH₂ H CH₃ OCH₃ H CH₃ H C₄H₉ — 195 H CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₃CH₂OCH₃ — 196 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 197 H CH₂ H CH₃ OCH₃ HCH₃ H OC₂H₅ — 198 H CH₂ H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 199 H CH₂ HCH₃ OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 200 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ C₂H₅  98-100 201 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 202 CH₃ O H CH₃ CH₃ H CH₃C₂H₅ C₄H₉ oil 203 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 204 CH₃ O H CH₃CH₃ H CH₃ C₂H₅ C₆H₅ — 205 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 206 CH₃ OH CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 207 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ — 208CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 209 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅CH₂CN — 210 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 211 CH₃ O H CH₃CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 212 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅CH₂N(CH₃)₂ — 213 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 214 CH₃ O H CH₃ CH₃H CH₃ c-C₃H₅ CH₂OCH₃ — 215 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 216 CH₃ OH CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 217 CH₃ O H CH₃ CH₃ H CH₃ H C₆H₅ — 218CH₃ O H CH₃ CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 219 CH₃ O H CH₃ CH₃ H CH₃ H2-Br—C₆H₄ — 220 CH₃ O H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ — 221 CH₃ O H CH₃ CH₃H CH₃ H 4-C₆H₅—C₆H₄ — 222 CH₃ O H CH₃ CH₃ H CH₃ H 2-(C₄H₉)—C₄H₈ — 223CH₃ O H CH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 224 CH₃ O H CH₃ CH₃ H CH₃ H(CH₂)₂OCH₃ — 225 CH₃ O H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 226 CH₃ O H CH₃ CH₃ HCH₃ H C₂H₅ — 227 CH₃ O H CH₃ CH₃ H CH₃ H C₃H₇ — 228 CH₃ O H CH₃ CH₃ HCH₃ H C₄H₉ — 229 CH₃ O H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 230 CH₃ O H CH₃CH₃ H CH₃ C₂H₅ OC₂H₅ — 231 CH₃ O H CH₃ CH₃ H CH₃ C₃H₇ OC₂H₅ — 232 CH₃ OH CH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 233 CH₃ O H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅— 234 CH₃ O H Cl Cl H H C₂H₅ C₂H₅ — 235 CH₃ O H Cl Cl H H C₂H₅ C₄H₉ —236 CH₃ O H Cl Cl H H C₂H₅ CH₂OCH₃ — 237 CH₃ O H Cl Cl H H C₂H₅ C₆H₅ —238 CH₃ O H Cl Cl H H C₂H₅ c-C₃H₅ — 239 CH₃ O H CI Cl H H C₂H₅ C₆H₁₃ —240 CH₃ O H Cl Cl H H C₂H₅ C₃H₇ — 241 CH₃ O H Cl Cl H H C₂H₅ (CH₂)₂OCH₃— 242 CH₃ O H Cl Cl H H C₂H₅ CH₂CN — 243 CH₃ O H Cl Cl H H C₂H₅(CH₂)₂—(Q1)^(b) — 244 CH₃ O H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 245 CH₃ OH Cl Cl H H C₂H₅ CH₂H(CH₃)₂ — 246 CH₃ O H Cl Cl H H c-C₃H₅ C₄H₉ — 247CH₃ O H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 248 CH₃ O H Cl Cl H H c-C₃H₅ C₆H₅ —249 CH₃ O H Cl Cl H H c-C₃H₅ c-C₃H₅ 132-134 250 CH₃ O H Cl Cl H H H C₆H₅— 251 CH₃ O H Cl Cl H H H 3-(CH₃O)—C₆H₄ — 252 CH₃ O H Cl Cl H H H2-Br—C₆H₄ — 253 CH₃ O H Cl Cl H H H 4-CH₃—C₆H₄ — 254 CH₃ O H Cl Cl H H H4-C₆H₅-C₆H₄ — 255 CH₃ O H Cl Cl H H H 2-(C₄H₉)—C₄H₉ — 256 CH₃ O H Cl ClH H H 3-(C₄H₉)—C₅H₁₀ — 257 CH₃ O H Cl Cl H H H (CH₂)₂OCH₃ — 258 CH₃ O HCl Cl H H H CH₂OCH₃ — 259 CH₃ O H Cl Cl H H H C₂H₅ — 260 CH₃ O H Cl Cl HH H C₃H₇ — 261 CH₃ O H Cl Cl H H H C₄H₉ — 262 CH₃ O H Cl Cl H H CH₂OCH₃CH₂OCH₃ — 263 CH₃ O H Cl Cl H H C₂H₅ OC₂H₅ — 264 CH₃ O H Cl Cl H H HOC₂H₅ — 265 CH₃ O H Cl Cl H H H O(CH₂)₂—OCH₃ — 266 CH₃ O H Cl Cl H HCH₂OCH₃ C₆H₅ — 267 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 268 CH₃ O H CH₃OCH₃ H CH₃ C₂H₅ C₄H₉ — 269 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 270 CH₃O H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 271 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅ —272 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 273 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅C₃H₇ — 274 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 275 CH₃ O H CH₃ OCH₃H CH₃ C₂H₅ CH₂CN — 276 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 277CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 278 CH₃ O H CH₃ OCH₃ H CH₃C₂H₅ CH₂N(CH₃)₂ — 279 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 280 CH₃ O HCH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 281 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ —282 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 283 CH₃ O H CH₃ OCH₃ H CH₃ HC₆H₅ — 284 CH₃ O H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 285 CH₃ O H CH₃ OCH₃H CH₃ H 2-Br—C₆H₄ — 286 CH₃ O H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 287 CH₃ OH CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 288 CH₃ O H CH₃ OCH₃ H CH₃ H2-(C₄H₉)—C₄H₉ — 289 CH₃ O H CH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 290 CH₃ OH CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 291 CH₃ O H CH₃ OCH₃ H CH₃ H CH₂OCH₃ —292 CH₃ O H CH₃ OCH₃ H CH₃ H C₂H₅ — 293 CH₃ O H CH₃ OCH₃ H CH₃ H C₃H₇ —294 CH₃ O H CH₃ OCH₃ H CH₃ H C₄H₉ — 295 CH₃ O H CH₃ OCH₃ H CH₃ CH₂OCH₃CH₂OCH₃ — 296 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 297 CH₃ O H CH₃ OCH₃ HCH₃ H OC₂H₅ — 298 CH₃ O H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 299 CH₃ O HCH₃ OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 300 CH₃ CH₂ CH₃ H Cl H H c-C₃H₅ c-C₃H₅106-109 301 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 302 CH₃ S H CH₃ CH₃ H CH₃C₂H₅ C₄H₉ — 303 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 304 CH₃ S H CH₃ CH₃H CH₃ C₂H₅ C₆H₅ — 305 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 306 CH₃ S HCH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 307 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ — 308 CH₃S H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 309 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN— 310 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 311 CH₃ S H CH₃ CH₃ HCH₃ C₂H₅ (CH₂)₂—(Q1)^(c) — 312 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ —313 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 314 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅CH₂OCH₃ — 315 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 316 CH₃ S H CH₃ CH₃ HCH c-C₃H₅ c-C₃H₅ — 317 CH₃ S H CH₃ CH₃ H CH₃ H C₆H₅ — 318 CH₃ S H CH₃CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 319 CH₃ S H CH₃ CH₃ H CH₃ H 2-Br—C₆H₄ — 320CH₃ S H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ — 321 CH₃ S H CH₃ CH₃ H CH₃ H4-C₆H₅—C₆H₄ — 322 CH₃ S H CH₃ CH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 323 CH₃ S HCH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 324 CH₃ S H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃— 325 CH₃ S H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 326 CH₃ S H CH₃ CH₃ H CH₃ H C₂H₅— 327 CH₃ S H CH₃ CH₃ H CH₃ H C₃H₇ — 328 CH₃ S H CH₃ CH₃ H CH₃ H C₄H₉ —329 CH₃ S H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 330 CH₃ S H CH₃ CH₃ H CH₃C₂H₅ OC₂H₅ — 331 CH₃ S H CH₃ CH₃ H CH₃ H OC₂H₅ — 332 CH₃ S H CH₃ CH₃ HCH₃ H O(CH₂)₂—OCH₃ — 333 CH₃ S H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ — 334 CH₃ SH Cl Cl H H C₂H₅ C₂H₅ — 335 CH₃ S H Cl Cl H H C₂H₅ C₄H₉ — 336 CH₃ S H ClCl H H C₂H₅ CH₂OCH₃ — 337 CH₃ S H Cl Cl H H C₂H₅ C₆H₅ — 338 CH₃ S H ClCl H H C₂H₅ c-C₃H₅ — 339 CH₃ S H Cl Cl H H C₂H₅ C₆H₁₃ — 340 CH₃ S H ClCl H H C₂H₅ C₃H₇ — 341 CH₃ S H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 342 CH₃ S HCl Cl H H C₂H₅ CH₂CN — 343 CH₃ S H Cl Cl H H C₂H₆ (CH₂)₂—(Q1)^(b) — 344CH₃ S H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 345 CH₃ S H Cl Cl H H C₂H₅CH₂N(CH₃)₂ — 346 CH₃ S H Cl Cl H H c-C₃H₅ C₄H₉ — 347 CH₃ S H Cl Cl H Hc-C₃H₅ CH₂OCH₃ — 348 CH₃ S H Cl Cl H H c-C₃H₅ C₆H₅ — 349 CH₃ S H Cl Cl HH c-C₃H₅ c-C₃H₅ — 350 CH₃ S H Cl Cl H H H C₆H₅ — 351 CH₃ S H Cl Cl H H H3-(CH₃O)—C₆H₄ — 352 CH₃ S H Cl Cl H H H 2-Br—C₆H₄ — 353 CH₃ S H Cl Cl HH H 4-CH₃—C₆H₄ — 354 CH₃ S H Cl Cl H H H 4-C₆H₅—C₆H₄ — 355 CH₃ S H Cl ClH H H 2-(C₄H₉)—C₄H₈ — 356 CH₃ S H Cl Cl H H H 3-(C₄H₉)—C₅H₁₀ — 357 CH₃ SH Cl Cl H H H (CH₂)₂OCH₃ — 358 CH₃ S H Cl Cl H H H CH₂OCH₃ — 359 CH₃ S HCl Cl H H H C₂H₅ — 360 CH₃ S H Cl Cl H H H C₃H₇ — 361 CH₃ S H Cl Cl H HH C₄H₉ — 362 CH₃ S H Cl Cl H H CH₂OCH₃ CH₂OCH₃ — 363 CH₃ S H Cl Cl H HC₂H₅ OC₂H₅ — 364 CH₃ S H Cl Cl H H H OC₂H₅ — 365 CH₃ S H Cl Cl H H HO(CH₂)₂—OCH₃ — 366 CH₃ S H Cl Cl H H CH₂OCH₃ C₆H₅ — 367 CH₃ S H CH₃ OCH₃H CH₃ C₂H₅ C₂H₅ — 368 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₄H₉ — 369 CH₃ S H CH₃OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 370 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 371 CH₃S H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅ — 372 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ —373 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₃H₇ — 374 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅(CH₂)₂OCH₃ — 375 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 376 CH₃ S H CH₃OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 377 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅(CH₂)₂—(Q2)^(c) — 378 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 379 CH₃ SH CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 380 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃— 381 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ — 382 CH₃ S H CH₃ OCH₃ H CH₃c-C₃H₅ c-C₃H₅ — 383 CH₃ S H CH₃ OCH₃ H CH₃ H C₆H₅ — 384 CH₃ S H CH₃ OCH₃H CH₃ H 3-(CH₃O)—C₆H₄ — 385 CH₃ S H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 386 CH₃S H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 387 CH₃ S H CH₃ OCH₃ H CH₃ H4-C₆H₅—C₆H₄ — 388 CH₃ S H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 389 CH₃ S HCH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 390 CH₃ S H CH₃ OCH₃ H CH₃ H(CH₂)₂OCH₃ — 391 CH₃ S H CH₃ OCH₃ H CH₃ H CH₂OCH₃ — 392 CH₃ S H CH₃ OCH₃H CH₃ H C₂H₅ — 393 CH₃ S H CH₃ OCH₃ H CH₃ H C₃H₇ — 394 CH₃ S H CH₃ OCH₃H CH₃ H C₄H₉ — 395 CH₃ S H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 396 CH₃ S HCH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 397 CH₃ S H CH₃ OCH₃ H CH₃ H OC₂H₅ — 398 CH₃S H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 399 CH₃ S H CH₃ OCH₃ H CH₃ CH₂OCH₃C₆H₅ — 400 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ c-C₃H₅ 153-156 401 CH₃ CH₂ CH₃ CH₃CH₃ H CH₃ C₂H₅ C₂H₅ — 402 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ 107-108403 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ 187-188 404 CH₃ CH₂ CH₃ CH₃CH₃ H CH₃ H C₄H₉ oil 405 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 98-99 406CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ H C₆H₅ 149-150 407 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃C₂H₅ (CH₂)₂OCH₃ — 408 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 409 CH₃CH₂ CH₃ CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 410 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃C₂H₅ CH₂OCH₃ — 411 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₂H₅ — 412 CH₃ CH₂ H CH₃ ClH H c-C₃H₅ C₄H₉ — 413 CH₃ CH₂ H CH₃ Cl H H c-C₃H₅ c-C₃H₅ 139-140 414 CH₃CH₂ H CH₃ Cl H H CH₃ C₃H₇ oil (A, C) 415 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₄H₉oil 416 CH₃ CH₂ H CH₂ Cl H H H C₆H₅ — 417 CH₃ CH₂ H CH₃ Cl H H C₂H₅(CH₂)₂OCH₃ — 418 CH₃ CH₂ H CH₃ Cl H H H (CH₂)₂OCH₃ — 419 CH₃ CH₂ H CH₃Cl H H CH₂OCH₃ CH₂OCH₃ — 420 CH₃ CH₂ H CH₃ Cl H H C₂H₅ CH₂OCH₃ — 421 CH₃CH₂ H Cl CH₃ H H C₂H₅ C₂H₅ — 422 CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ C₄H₉ — 423CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ c-C₃H₅ 177-178 424 CH₃ CH₂ H Cl CH₃ H H CH₃C₃H₇ oil 425 CH₃ CH₂ H Cl CH₃ H H C₂H₅ C₄H₉ — 426 CH₃ CH₂ H Cl CH₃ H H HC₆H₅ — 427 CH₃ CH₂ H Cl CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 428 CH₃ CH₂ H Cl CH₃ HH H (CH₂)₂OCH₃ — 429 CH₃ CH₂ H Cl CH₃ H H CH₂OCH₃ CH₂OCH₃ — 430 CH₃ CH₂H Cl CH₃ H H C₂H₅ CH₂OCH₃ — 431 CH₃ CH₂ H Cl Cl H OCH₃ C₃H₇ c-C₃H₅141-144 432 CH₃ CH₂ H CH₃ CH₃ H OCH₃ C₂H₅ C₃H₇ 108-110 433 CH₃ CH₂ H ClCl H CH₃ c-C₃H₅ c-C₃H₅ 194-195 434 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅c-C₃H₅CH₂ oil 435 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OH 155-157 436 CH₃ CH₂H CH₃ OCH₃ H H C₂H₅ c-C₃H₅CH₂ oil 437 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ C₃H₇oil 438 CH₃ CH₂ H CH₃ OCH₃ H H H 4-(CH₃O)—C₆H₄ oil 439 CH₃ CH₂ H CH₃OCH₃ H H C₂H₅ c-C₃H₅ oil 440 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ C₅H₁₁ oil 441CH₃ CH₂ H Cl NMe₂ H H C₂H₅ C₂H₅ — 442 CH₃ CH₂ H Cl NMe₂ H H c-C₃H₅ C₄H₉— 443 CH₃ CH₂ H Cl NMe₂ H H c-C₃H₅ c-C₃H₅ — 444 CH₃ CH₂ H Cl NMe₂ H H HC₃H₇ — 445 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ C₄H₉ — 446 CH₃ CH₂ H Cl NMe₂ H H HC₆H₅ — 447 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ (CH₂)₂OCH₃ — 448 CH₃ CH₂ H Cl NMe₂H H H (CH₂)₂OCH₃ — 449 CH₃ CH₂ H Cl NMe₂ H H CH₂OCH₃ CH₂OCH₃ — 450 CH₃CH₂ H Cl NMe₂ H H C₂H₅ CH₂OCH₃ — 451 CH₃ CH₂ H CH₃ NMe₂ H H C₂H₅ C₂H₅ —452 CH₃ CH₂ H CH₃ NMe₂ H H c-C₃H₅ C₄H₉ — 453 CH₃ CH₂ H CH₃ NMe₂ H Hc-C₃H₅ c-C₃H₅ — 454 CH₃ CH₂ H CH₃ NMe₂ H H H C₃H₇ — 455 CH₃ CH₂ H CH₃NMe₂ H H C₂H₅ C₄H₉ — 456 CH₃ CH₂ H CH₃ NMe₂ H H H C₆H₅ — 457 CH₃ CH₂ HCH₃ NMe₂ H H C₂H₅ (CH₂)₂OCH₃ — 458 CH₃ CH₂ H CH₃ NMe₂ H H H (CH₂)₂OCH₃ —459 CH₃ CH₂ H CH₃ NMe₂ H H CH₂OCH₃ CH₂OCH₃ — 460 CH₃ CH₂ H CH₃ NMe₂ H HC₂H₅ CH₂OCH₃ — 461 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 462 CH₃ CH₂NMe₂ CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 463 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ c-C₃H₅c-C₃H₅ — 464 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ H C₃H₇ — 465 CH₃ CH₂ NMe₂ CH₃CH₃ H CH₃ C₂H₅ C₄H₉ — 466 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ H C₆H₅ — 467 CH₃CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 468 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃H (CH₂)₂OCH₃ — 469 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 470 CH₃CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 471 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅C₂H₅ — 472 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 473 C₂H₅ CH₂ H CH₃ CH₃H CH₃ c-C₃H₅ c-C₃H₅ — 474 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ H C₃H₇ — 475 C₂H₅ CH₂H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 92-95 476 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ —477 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 478 C₂H₅ CH₂ H CH₃ CH₃ HCH₃ H (CH₂)₂OCH₃ — 479 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 480C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 481 CH₃ CHCH₃ H CH₃ CH₃ H CH₃C₂H₅ C₂H₅ — 482 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 483 CH₃ CHCH₃ HCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 484 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ H C₃H₇ — 485CH₃ CHCH₃ H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 486 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ HC₆H₅ — 487 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 488 CH₃ CHCH₃ HCH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 489 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ CH₂OCH₃CH₂OCH₃ — 490 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 491 CH₃ CH₂ H CH₃CH₃ H H C₂H₅ C₂H₅ 96-97 492 CH₃ CH₂ H CH₃ CH₃ H H c-C₃H₅ C₄H₉ — 493 CH₃CH₂ H CH₃ CH₃ H H c-C₃H₅ c-C₃H₅ 149-150 494 CH₃ CH₂ H CH₃ CH₃ H H H C₃H₇ 99-100 495 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ C₄H₉ — 496 CH₃ CH₂ H CH₃ CH₃ H HH C₆H₅ — 497 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 498 CH₃ CH₂ H CH₃CH₃ H H H (CH₂)₂OCH₃ — 499 CH₃ CH₂ H CH₃ CH₃ H H CH₂OCH₃ CH₂OCH₃ — 500CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ CH₂OCH₃ — 501 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃C₃H₇ — 502 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ C₄H₉ oil 503 CH₃ CH₂ H CH₃ CH₃ HCH₃ CH₃ C₅H₁₁ oil 504 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ 2-C₄H₉ 109-110 505CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OC₂H₅ — 506 CH₃ CH₂ H Cl Cl H H CH₃ C₃H₇oil (A, B, C) 507 CH₃ CH₂ H Cl Cl H H CH₃ C₄H₉ oil 508 CH₃ CH₂ H Cl Cl HH CH₃ C₅H₁₁ — 509 CH₃ CH₂ H Cl Cl H H C₂H₅ 2-C₄H₉ — 510 CH₃ CH₂ H Cl ClH H C₂H₅ CH₂OC₂H₅ — 511 CH₃ CH₂ H Cl CF₃ H H C₂H₅ c-C₃H₅ oil (A) 78-80(B) 116-117 (C) 512 CH₃ CH₂ H Cl CF₃ H H c-C₃H₅ c-C₃H₅ 145-146 513 CH₃CH₂ H Cl CF₃ H H C₂H₅ C₄H₉ oil 514 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₂H₅ oil515 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂OC₂H₅ — 516 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅c-C₃H₅ — 517 CH₃ CH₂ H OCH₃ Cl H Cl c-C₃H₅ c-C₃H₅ 183-184 518 CH₃ CH₂ HOCH₃ Cl H Cl C₂H₅ C₄H₉ 109-110 519 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅(CH₂)₂OCH₃ — 520 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ CH₂OC₂H₅ — 521 CH₃ CH₂ HCH₃ CH₃ H CH₃ C₃H₇ C₃H₇ 115-120 522 CH₃ O H CH₃ CH₃ H CH₃ C₃H₇ C₃H₇ —523 CH₃ CH₂ H Cl Cl H H C₃H₇ C₃H₇  99-101 524 CH₃ CH₂ H CH₃ OCH₃ H HC₃H₇ C₃H₇ oil 525 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₃H₇ C₃H₇ 109-111 526 CH₃ CH₂H CH₃ Cl H H C₃H₇ C₃H₇ oil 527 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₃H₇ C₃H₇ — 528CH₃ CH₂ H Cl CF₃ H H C₃H₇ C₃H₇ oil 529 CH₃ CH₂ H Cl CF₃ H Cl C₃H₇ C₃H₇ —530 CH₃ CH₂ H OCH₃ Cl H Cl C₃H₇ C₃H₇ 129-131 531 CH₃ CH₂ H CH₃ CH₃ H CH₃CH₃ (CH₃)₂CHCH₂ 77-85 532 CH₃ O H CH₃ CH₃ H CH₃ CH₃ (CH₃)₂CHCH₂ — 533CH₃ CH₂ H Cl Cl H H CH₃ (CH₃)₂CHCH₂ — 534 CH₃ CH₂ H CH₃ OCH₃ H H CH₃(CH₃)₂CHCH₂ — 535 CH₃ CH₂ H OCH₃ CH₃ H CH₃ CH₃ (CH₃)₂CHCH₂ — 536 CH₃ CH₂H CH₃ Cl H H CH₃ (CH₃)₂CHCH₂ — 537 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃(CH₃)₂CHCH₂ — 538 CH₃ CH₂ H Cl CF₃ H H C₂H₅ (CH₃)₂CH oil 539 CH₃ CH₂ HCl CF₃ H Cl CH₃ (CH₃)₂CHCH₂ — 540 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ (CH₃)₂CHCH₂— 541 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ c-C₃H₅ 118-127 542 CH₃ O H CH₃ CH₃ HCH₃ CH₃ c-C₃H₅ — 543 CH₃ CH₂ H Cl Cl H H CH₃ c-C₃H₅ oil 544 CH₃ CH₂ HCH₃ OCH₃ H H CH₃ c-C₃H₅ oil 545 CH₃ CH₂ H OCH₃ CH₃ H CH₃ CH₃ c-C₃H₅ —546 CH₃ CH₂ H CH₃ Cl H H CH₃ c-C₃H₅ — 547 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃c-C₃H₅ — 548 CH₃ CH₂ H Cl CF₃ H H CH₃ c-C₃H₅ oil 549 CH₃ CH₂ H Cl CF₃ HCl CH₃ c-C₃H₅ — 550 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ c-C₃H₅ — 551 CH₃ CH₂ HCH₃ CH₃ H CH₃ CH₃ CH₃ oil 552 CH₃ O H CH₃ CH₃ H CH₃ CH₃ CH₃ — 553 CH₃CH₂ H Cl Cl H H CH₃ CH₃ — 554 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ CH₃ — 555 CH₃CH₂ H OCH₃ CH₃ H CH₃ CH₃ CH₃ — 556 CH₃ CH₂ H CH₃ Cl H H CH₃ CH₃ — 557CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ CH₃ — 558 CH₃ CH₂ H Cl CF₃ H H CH₃ C₄H₉ oil559 CH₃ CH₂ H Cl CF₃ H Cl CH₃ CH₃ — 560 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ CH₃ —561 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₅H₁₁ 102-103 562 CH₃ O H CH₃ CH₃ H CH₃C₂H₅ C₅H₁₁ — 563 CH₃ CH₂ H Cl Cl H H C₂H₅ C₅H₁₁ — 564 CH₃ CH₂ H CH₃ OCH₃H H C₂H₅ C₄H₉ oil 565 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₅H₁₁ — 566 CH₃ CH₂H CH₃ Cl H H C₂H₅ C₅H₁₁ — 567 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₅H₁₁ — 568CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₅H₁₁ — 569 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₅H₁₁ —570 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₅H₁₁ — 571 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅C₂H₅(CH₂)₂ oil 572 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅(CH₂)₂ — 573 CH₃ CH₂ HCl Cl H H C₂H₅ C₂H₅(CH₂)₂ — 574 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₂H₅(CH₂)₂ —575 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₂H₅(CH₂)₂ — 576 CH₃ CH₂ H CH₃ Cl H HC₂H₅ C₂H₅(CH₂)₂ — 577 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₂H₅(CH₂)₂ — 578 CH₃CH₂ H Cl CF₃ H H C₂H₅ C₂H₅(CH₂)₂ — 579 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅C₂H₅(CH₂)₂ — 580 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₂H₅(CH₂)₂ — 581 CH₃ CH₂ HCH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂ oil 582 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂— 583 CH₃ CH₂ H Cl Cl H H C₂H₅ C₂H₅OCH₂ — 584 CH₃ CH₂ H CH₃ OCH₃ H HC₂H₅ C₂H₅OCH₂ — 585 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂ — 586 CH₃ CH₂H CH₃ Cl H H C₂H₅ C₂H₅OCH₂ — 587 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₂H₅OCH₂ —588 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₂H₅OCH₂ — 589 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅C₂H₅OCH₂ — 590 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₂H₅OCH₂ — 591 CH₃ CH₂ H CH₃CH₃ H CH₃ H c-C₃H₅CH(OMe) oil (CH₂)₂ 592 CH₃ O H CH₃ CH₃ H CH₃ Hc-C₃H₅CH(OMe) — (CH₂)₂ 593 CH₃ CH₂ H Cl Cl H H H c-C₃H₅CH(OMe) — (CH₂)₂594 CH₃ CH₂ H CH₃ OCH₃ H H H c-C₃H₅CH(OMe) — (CH₂)₂ 595 CH₃ CH₂ H OCH₃CH₃ H CH₃ H c-C₃H₅CH(OMe) — (CH₂)₂ 596 CH₃ CH₂ H CH₃ Cl H H Hc-C₃H₅CH(OMe) — (CH₂)₂ 597 CH₃ CH₂ H CH₃ CH₃ CH₃ H H c-C₃H₅CH(OMe) —(CH₂)₂ 598 CH₃ CH₂ H Cl CF₃ H H H c-C₃H₅CH(OMe) — (CH₂)₂ 599 CH₃ CH₂ HCl CF₃ H Cl H c-C₃H₅CH(OMe) — (CH₂)₂ 600 CH₃ CH₂ H OCH₃ Cl H Cl Hc-C₃H₅CH(OMe) — (CH₂)₂ 601 CH₃ CH₂ CH₃ Cl Cl H H C₂H₅ C₂H₅ — 602 CH₃ CH₂CH₃ Cl Cl H H c-C₃H₅ C₄H₉ — 603 CH₃ CH₂ CH₃ Cl Cl H H c-C₃H₅ c-C₃H₅155-156 604 CH₃ CH₂ CH₃ Cl Cl H H H C₄H₉ — 605 CH₃ CH₂ CH₃ Cl Cl H HC₂H₅ C₄H₉ — 606 CH₃ CH₂ CH₃ Cl Cl H H H C₆H₅ — 607 CH₃ CH₂ CH₃ Cl CI H HC₂H₅ (CH₂)₂OCH₃ — 608 CH₃ CH₂ CH₃ Cl Cl H H CH₃ C₄H₉ — 609 CH₃ CH₂ CH₃Cl Cl H H C₃H₇ C₃H₇ — 610 CH₃ CH₂ CH₃ Cl Cl H H C₂H₅ C₃H₇ — 611 CH₃ CH₂CH₃ OCH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 612 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ c-C₃H₅C₄H₉ — 613 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 614 CH₃ CH₂ CH₃OCH₃ CH₃ H CH₃ H C₄H₉ — 615 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 616CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ H C₆H₅ — 617 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ C₂H₅(CH₂)₂OCH₃ — 618 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 619 CH₃ CH₂ CH₃OCH₃ CH₃ H CH₃ C₃H₇ C₃H₇ — 620 CH₃ CH₂ CH₃ OCH₃ CH₃ H CH₃ C₂H₅ C₃H₇ —621 CH₃ CH₂ CH₃ CH₃ OCH₃ H H C₂H₅ C₂H₅ — 622 CH₃ CH₂ CH₃ CH₃ OCH₃ H Hc-C₃H₅ C₄H₉ — 623 CH₃ CH₂ CH₃ CH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ — 624 CH₃ CH₂CH₃ CH₃ OCH₃ H H H C₄H₉ — 625 CH₃ CH₂ CH₃ CH₃ OCH₃ H H C₂H₅ C₄H₉ — 626CH₃ CH₂ CH₃ CH₃ OCH₃ H H H C₆H₅ — 627 CH₃ CH₂ CH₃ CH₃ OCH₃ H H C₂H₅(CH₂)₂OCH₃ — 628 CH₃ CH₂ CH₃ CH₃ OCH₃ H H CH₃ C₄H₉ — 629 CH₃ CH₂ CH₃ CH₃OCH₃ H H C₃H₇ C₃H₇ — 630 CH₃ CH₂ CH₃ CH₃ OCH₃ H H C₂H₅ C₃H₇ — 631 CH₃CH₂ CH₃ CH₃ Cl H H C₂H₅ C₂H₅ — 632 CH₃ CH₂ CH₃ CH₃ Cl H H c-C₃H₅ C₄H₉ —633 CH₃ CH₂ CH₃ CH₃ Cl H H c-C₃H₅ c-C₃H₅ — 634 CH₃ CH₂ CH₃ CH₃ Cl H H HC₄H₉ — 635 CH₃ CH₂ CH₃ CH₃ Cl H H C₂H₅ C₄H₉ — 636 CH₃ CH₂ CH₃ CH₃ Cl H HH C₆H₅ — 637 CH₃ CH₂ CH₃ CH₃ Cl H H C₂H₅ (CH₂)₂OCH₃ — 638 CH₃ CH₂ CH₃CH₃ Cl H H CH₃ C₄H₉ — 639 CH₃ CH₂ CH₃ CH₃ Cl H H C₃H₇ C₃H₇ — 640 CH₃ CH₂CH₃ CH₃ Cl H H C₂H₅ C₃H₇ — 641 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ C₂H₅ — 642CH₃ CH₂ CH₃ Cl CF₃ H H c-C₃H₅ C₄H₉ — 643 CH₃ CH₂ CH₃ Cl CF₃ H H c-C₃H₅c-C₃H₅ — 644 CH₃ CH₂ CH₃ Cl CF₃ H H H C₄H₉ — 645 CH₃ CH₂ CH₃ Cl CF₃ H HC₂H₅ C₄H₉ — 646 CH₃ CH₂ CH₃ Cl CF₃ H H H C₆H₅ — 647 CH₃ CH₂ CH₃ Cl CF₃ HH C₂H₅ (CH₂)₂OCH₃ — 648 CH₃ CH₂ CH₃ Cl CF₃ H H CH₃ C₄H₉ — 649 CH₃ CH₂CH₃ Cl CF₃ H H C₃H₇ C₃H₇ — 650 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ C₃H₇ — 651CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₂H₅ — 652 CH₃ CH₂ CH₃ Cl CF₃ H Cl c-C₃H₅C₄H₉ — 653 CH₃ CH₂ CH₃ Cl CF₃ H Cl c-C₃H₅ c-C₃H₅ — 654 CH₃ CH₂ CH₃ ClCF₃ H Cl H C₄H₉ — 655 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₄H₉ — 656 CH₃ CH₂CH₃ Cl CF₃ H Cl H C₆H₅ — 657 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ (CH₂)₂OCH₃ —658 CH₃ CH₂ CH₃ Cl CF₃ H Cl CH₃ C₄H₉ — 659 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₃H₇C₃H₇ — 660 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₃H₇ — 661 CH₃ CH₂ CH₃ OCH₃ Cl HCl C₂H₅ C₂H₅ — 662 CH₃ CH₂ CH₃ OCH₃ Cl H Cl c-C₃H₅ C₄H₉ — 663 CH₃ CH₂CH₃ OCH₃ Cl H Cl c-C₃H₅ c-C₃H₅ — 664 CH₃ CH₂ CH₃ OCH₃ Cl H Cl H C₄H₉ —665 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ C₄H₉ — 666 CH₃ CH₂ CH₃ OCH₃ Cl H Cl HC₆H₅ — 667 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ (CH₂)₂OCH₃ — 668 CH₃ CH₂ CH₃OCH₃ Cl H Cl CH₃ C₄H₉ — 669 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₃H₇ C₃H₇ — 670 CH₃CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ C₃H₇ — 671 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₂H₅ C₂H₅ —672 CH₃ CH₂ CH₃ CH₃ CH₃ H H c-C₃H₅ C₄H₉ — 673 CH₃ CH₂ CH₃ CH₃ CH₃ H Hc-C₃H₅ c-C₃H₅ — 674 CH₃ CH₂ CH₃ CH₃ CH₃ H H H C₄H₉ — 675 CH₃ CH₂ CH₃ CH₃CH₃ H H C₂H₅ C₄H₉ — 676 CH₃ CH₂ CH₃ CH₃ CH₃ H H H C₆H₅ — 677 CH₃ CH₂ CH₃CH₃ CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 678 CH₃ CH₂ CH₃ CH₃ CH₃ H H CH₃ C₄H₉ — 679CH₃ CH₂ CH₃ CH₃ CH₃ H H C₃H₇ C₃H₇ — 680 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₂H₅C₃H₇ — 681 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₄H₉ — 682 CH₃ CH₂ H OCH₃ CH₃ HCH₃ C₂H₅ C₄H₉ 107-109 683 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₄H₉ — 684 CH₃ CH₂H CH₃ CH₃ CH₃ H C₂H₅ C₄H₉ — 685 CH₃ CH₂ H CH₃ OCH₃ H H c-C₃H₅ c-C₃H₅101-103 686 CH₃ CH₂ H OCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ 187-188 687 CH₃ CH₂ HCl CF₃ H Cl c-C₃H₅ c-C₃H₅ — 688 CH₃ CH₂ H CH₃ CH₃ CH₃ H c-C₃H₅ c-C₃H₅119-121 689 CH₃ CH₂ H CH₃ OCH₃ H H H C₆H₅ 108-109 690 CH₃ CH₂ H OCH₃ CH₃H CH₃ H C₆H₅ oil 691 CH₃ CH₂ H Cl CF₃ H Cl H C₆H₅ — 692 CH₃ CH₂ H CH₃CH₃ CH₃ H H C₆H₅ oil 693 CH₃ CH₂ H CH₃ OCH₃ H H c-C₃H₅ C₄H₉ oil 694 CH₃CH₂ H OCH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 695 CH₃ CH₂ H Cl CF₃ H Cl c-C₃H₅ C₄H₉— 696 CH₃ CH₂ H CH₃ CH₃ CH₃ H c-C₃H₅ C₄H₉ — 697 CH₃ CH₂ H CH₃ OCH₃ H HCH₃ C₄H₉ oil 698 CH₃ CH₂ H OCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 699 CH₃ CH₂ H ClCF₃ H Cl CH₃ C₄H₉ — 700 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ C₄H₉ — 701 CH₃ O HCH₃ OCH₃ H H C₂H₅ C₄H₉ — 702 CH₃ O H OCH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 703 CH₃O H Cl CF₃ H Cl C₂H₅ C₄H₉ — 704 CH₃ O H CH₃ CH₃ CH₃ H C₂H₅ C₄H₉ — 705CH₃ O H CH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ — 706 CH₃ O H OCH₃ CH₃ H CH₃ c-C₃H₅c-C₃H₅ — 707 CH₃ O H Cl CF₃ H Cl c-C₃H₅ c-C₃H₅ — 708 CH₃ O H CH₃ CH₃ CH₃H c-C₃H₅ c-C₃H₅ — 709 CH₃ O H CH₃ OCH₃ H H H C₆H₅ — 710 CH₃ O H OCH₃ CH₃H CH₃ H C₆H₅ — 711 CH₃ O H Cl CF₃ H Cl H C₆H₅ — 712 CH₃ O H CH₃ CH₃ CH₃H H C₆H₅ — 713 CH₃ O H CH₃ OCH₃ H H c-C₃H₅ C₄H₉ — 714 CH₃ O H OCH₃ CH₃ HCH₃ c-C₃H₅ C₄H₉ — 715 CH₃ O H Cl CF₃ H Cl c-C₃H₅ C₄H₉ — 716 CH₃ O H CH₃CH₃ CH₃ H c-C₃H₅ C₄H₉ — 717 CH₃ O H CH₃ OCH₃ H H CH₃ C₄H₉ — 718 CH₃ O HOCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 719 CH₃ O H Cl CF₃ H Cl CH₃ C₄H₉ — 720 CH₃ O HCH₃ CH₃ CH₃ H CH₃ C₄H₉ — 721 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH(CH₃)₂146-147 722 CH₃ CH₂ H Cl Cl H H C₂H₅ CH(CH₃)₂ — 723 CH₃ CH₂ H Cl CH₃ H HC₂H₅ CH(CH₃)₂ — 724 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH(CH₃)₂ oil 725 CH₃ CH₂H CH₃ OCH₃ H H C₂H₅ CH(CH₃)₂ oil 726 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH(CH₃)₂— 727 CH₃ CH₂ H CF₃ Cl H H C₂H₅ CH(CH₃)₂ oil 728 CH₃ CH₂ H CH₃ Cl H HC₂H₅ CH(CH₃)₂ — 729 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ CH(CH₃)₂ — 730 CH₃ CH₂ HCl CN H H C₂H₅ CH(CH₃)₂ — 731 CH₃ CH₂ H Cl Cl F H C₂H₅ CH(CH₃)₂ — 732CH₃ CH₂ H Cl Cl Cl H C₂H₅ CH(CH₃)₂ — 733 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅CH(CH₃)₂ — 734 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ CH(CH₃)₂ — 735 CH₃ CH₂ H ClCH₃ F H C₂H₅ CH(CH₃)₂ — 736 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ CH(CH₃)₂ — 737CH₃ CH₂ H Cl CF₃ F H C₂H₅ CH(CH₃)₂ — 738 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅CH(CH₃)₂ — 739 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ CH(CH₃)₂ — 740 CH₃ CH₂ H ClOCH₃ CH₃ H C₂H₅ CH(CH₃)₂ — 741 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ CH(CH₃)₂ —742 CH₃ CH₂ H Cl H Cl H C₂H₅ CH(CH₃)₂ — 743 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅CH(CH₃)₂ — 744 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ CH(CH₃)₂ — 745 CH₃ CH₂ H CH₃Cl OCH₃ H C₂H₅ CH(CH₃)₂ — 746 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ CH(CH₃)₂ —747 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₃H₇ c-C₃H₅ 140-143 748 CH₃ CH₂ H Cl Cl H HC₃H₇ c-C₃H₅ 107-108 (A) 79-82 (C) 749 CH₃ CH₂ H Cl CH₃ H H C₃H₇ c-C₃H₅106-108 750 CH₃ CH₂ H Cl OCH₃ H H C₃H₇ c-C₃H₅ oil 751 CH₃ CH₂ H CH₃ OCH₃H H C₃H₇ c-C₃H₅ oil 752 CH₃ CH₂ H Cl CF₃ H H C₃H₇ c-C₃H₅ 108-109 753 CH₃CH₂ H CF₃ Cl H H C₃H₇ c-C₃H₅ oil (A) 95-97 (C) 754 CH₃ CH₂ H CH₃ Cl H HC₃H₇ c-C₃H₅ 87-88 755 CH₃ CH₂ H CF₃ CF₃ H H C₃H₇ c-C₃H₅ — 756 CH₃ CH₂ HCl CN H H C₃H₇ c-C₃H₅ — 757 CH₃ CH₂ H Cl Cl F H C₃H₇ c-C₃H₅ — 758 CH₃CH₂ H Cl Cl Cl H C₃H₇ c-C₃H₅ — 759 CH₃ CH₂ H CH₃ OCH₃ F H C₃H₇ c-C₃H₅ —760 CH₃ CH₂ H CH₃ OCH₃ Cl H C₃H₇ c-C₃H₅ — 761 CH₃ CH₂ H Cl CH₃ F H C₃H₇c-C₃H₅ — 762 CH₃ CH₂ H Cl CF₃ Cl H C₃H₇ c-C₃H₅ — 763 CH₃ CH₂ H Cl CF₃ FH C₃H₇ c-C₃H₅ — 764 CH₃ CH₂ H Cl OCH₃ Cl H C₃H₇ c-C₃H₅ — 765 CH₃ CH₂ HCl OCH₃ F H C₃H₇ c-C₃H₅ — 766 CH₃ CH₂ H Cl OCH₃ CH₃ H C₃H₇ c-C₃H₅ — 767CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₃H₇ c-C₃H₅ oil 768 CH₃ CH₂ H Cl H Cl H C₃H₇c-C₃H₅ — 769 CH₃ CH₂ H Cl Cl OCH₃ H C₃H₇ c-C₃H₅ — 770 CH₃ CH₂ H Cl CH₃OCH₃ H C₃H₇ c-C₃H₅ — 771 CH₃ CH₂ H CH₃ Cl OCH₃ H C₃H₇ c-C₃H₅ — 772 CH₃CH₂ H CH₃ CH₃ OCH₃ H C₃H₇ c-C₃H₅ — 773 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ CH₂Cl109-110 774 CH₃ CH₂ H Cl Cl H H C₂H₅ C₃H₇ — 775 CH₃ CH₂ H Cl CH₃ H HC₂H₅ C₃H₇ — 776 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₃H₇ oil 777 CH₃ CH₂ H CH₃OCH₃ H H C₂H₅ C₃H₇ oil 778 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₃H₇ oil 779 CH₃CH₂ H CF₃ Cl H H C₂H₅ C₃H₇ oil 780 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₃H₇ — 781CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₃H₇ — 782 CH₃ CH₂ H Cl CN H H C₂H₅ C₃H₇ —783 CH₃ CH₂ H Cl Cl F H C₂H₅ C₃H₇ — 784 CH₃ CH₂ H Cl Cl Cl H C₂H₅ C₃H₇ —785 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₃H₇ — 786 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅C₃H₇ — 787 CH₃ CH₂ H Cl CH₃ F H C₂H₅ C₃H₇ — 788 CH₃ CH₂ H Cl CF₃ Cl HC₂H₅ C₃H₇ — 789 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₃H₇ — 790 CH₃ CH₂ H Cl OCH₃Cl H C₂H₅ C₃H₇ — 791 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₃H₇ — 792 CH₂ CH₃ H ClOCH₃ CH₃ H C₂H₅ C₃H₇ — 793 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ C₃H₇ oil 794CH₃ CH₂ H Cl H Cl H C₂H₅ C₃H₇ — 795 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ C₃H₇ —796 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ C₃H₇ — 797 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅C₃H₇ — 798 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ C₃H₇ — 799 CH₃ CH₂ H CH₃ CH₃CH₃ H C₂H₅ C₃H₇ oil 800 CH₃ CH₂ H CF₃ Cl H H H 4-CH₃O—C₆H₄ 138-139 801CH₃ CH₂ H CF₃ Cl H H c-C₃H₅ c-C₃H₅ 138-139 802 CH₃ CH₂ H CF₃ Cl H H C₂H₅c-C₃H₅ oil (A) 122-125 (C) 803 CH₃ CH₂ H CF₃ Cl H H CH₃ c-C₃H₅ oil 804CH₃ CH₂ H CF₃ Cl H H CH₃ C₃H₇ oil 805 CH₃ CH₂ H CF₃ Cl H H CH₃ C₄H₉ oil806 CH₃ CH₂ H CF₃ Cl H H CH₃ C₅H₁₁ — 807 CH₃ CH₂ H CF₃ Cl H H C₂H₅ C₄H₉oil 808 CH₃ CH₂ H CF₃ Cl H H C₃H₇ C₃H₇ oil 809 CH₃ CH₂ H CF₃ Cl H H C₂H₅C₂H₅ oil 810 CH₃ CH₂ H Cl CN H H H 4-CH₃O—C₆H₄ — 811 CH₃ CH₂ H Cl CN H Hc-C₃H₅ c-C₃H₅ 180-182 812 CH₃ CH₂ H Cl CN H H C₂H₅ c-C₃H₅ — 813 CH₃ CH₂H Cl CN H H CH₃ c-C₃H₅ — 814 CH₃ CH₂ H Cl CN H H CH₃ C₃H₇ — 815 CH₃ CH₂H Cl CN H H CH₃ C₄H₉ — 816 CH₃ CH₂ H Cl CN H H CH₃ C₅H₁₁ — 817 CH₃ CH₂ HCl CN H H C₂H₅ C₄H₉ — 818 CH₃ CH₂ H Cl CN H H C₃H₇ C₃H₇ — 819 CH₃ CH₂ HCl CN H H C₂H₅ C₂H₅ — 820 CH₃ CH₂ H CF₃ CF₃ H H H 4-CH₃O—C₆H₄ — 821 CH₃CH₂ H CF₃ CF₃ H H C-C₃H₅ c-C₃H₅ 149-150 822 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅c-C₃H₅ — 823 CH₃ CH₂ H CF₃ CF₃ H H CH₃ c-C₃H₅ — 824 CH₃ CH₂ H CF₃ CF₃ HH CH₃ C₃H₇ oil 825 CH₃ CH₂ H CF₃ CF₃ H H CH₃ C₄H₉ — 826 CH₃ CH₂ H CF₃CF₃ H H CH₃ C₅H₁₁ — 827 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₄H₉ — 828 CH₃ CH₂ HCF₃ CF₃ H H C₃H₇ C₃H₇ — 829 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₂H₅ — 830 CH₃CH₂ H Cl OCH₃ H H H 4-CH₃O—C₆H₄ 58-60 831 CH₃ CH₂ H Cl OCH₃ H H c-C₃H₅c-C₃H₅ 139-140 832 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ c-C₃H₅ oil 833 CH₃ CH₂ HCl OCH₃ H H H c-C₃H₅ oil 834 CH₃ CH₂ H Cl OCH₃ H H CH₃ C₃H₇ oil 835 CH₃CH₂ H Cl OCH₃ H H CH₃ C₄H₉ oil 836 CH₃ CH₂ H Cl OCH₃ H H CH₃ C₅H₁₁ oil837 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ C₄H₉ oil 838 CH₃ CH₂ H Cl OCH₃ H H C₃H₇C₃H₇ oil 839 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ C₂H₅ oil 840 CH₃ CH₂ H Cl Cl H HH 4-CH₃O—C₆H₄ — 841 CH₃ CH₂ H Cl Cl F H c-C₃H₅ c-C₃H₅ 148-149 842 CH₃CH₂ H Cl Cl F H C₂H₅ c-C₃H₅ — 843 CH₃ CH₂ H Cl Cl F H CH₃ c-C₃H₅ — 844CH₃ CH₂ H Cl Cl F H CH₃ C₃H₇ — 845 CH₃ CH₂ H Cl Cl F H CH₃ C₄H₉ — 846CH₃ CH₂ H Cl Cl F H CH₃ C₅H₁₁ — 847 CH₃ CH₂ H Cl Cl F H C₂H₅ C₄H₉ — 848CH₃ CH₂ H Cl Cl F H C₃H₇ C₃H₇ — 849 CH₃ CH₂ H Cl Cl F H C₂H₅ C₂H₅ — 850CH₃ CH₂ H Cl Cl Cl H H 4-CH₃O—C₆H₅ — 851 CH₃ CH₂ H Cl Cl Cl H c-C₃H₅c-C₃H₅ — 852 CH₃ CH₂ H Cl Cl Cl H C₂H₅ c-C₃H₅ — 853 CH₃ CH₂ H Cl Cl Cl HCH₃ c-C₃H₅ — 854 CH₃ CH₂ H Cl Cl Cl H CH₃ C₃H₇ — 855 CH₃ CH₂ H Cl Cl ClH CH₃ C₄H₉ — 856 CH₃ CH₂ H Cl Cl Cl H CH₃ C₅H₁₁ — 857 CH₃ CH₂ H Cl Cl ClH C₂H₅ C₄H₉ — 858 CH₃ CH₂ H Cl Cl Cl H C₃H₇ C₃H₇ — 859 CH₃ CH₂ H Cl ClCl H C₂H₅ C₂H₅ — 860 CH₃ CH₂ H CH₃ OCH₃ F H H 4-CH₃O—C₆H₄ — 861 CH₃ CH₂H CH₃ OCH₃ F H c-C₃H₅ c-C₃H₅ 128-129 862 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅c-C₃H₅ — 863 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ c-C₃H₅ — 864 CH₃ CH₂ H CH₃ OCH₃F H CH₃ C₃H₇ — 865 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ C₄H₉ — 866 CH₃ CH₂ H CH₃OCH₃ F H CH₃ C₅H₁₁ — 867 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₄H₉ — 868 CH₃ CH₂H CH₃ OCH₃ F H C₃H₇ C₃H₇ — 869 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₂H₅ — 870CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-CH₃O—C₆H₄ oil 871 CH₃ CH₂ H CH₃ OCH₃ Cl Hc-C₃H₅ c-C₃H₅ 179-181 872 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ c-C₃H₅ — 873 CH₃CH₂ H CH₃ OCH₃ Cl H CH₃ c-C₃H₅ — 874 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ C₃H₇ —875 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ C₄H₉ — 876 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃C₅H₁₁ — 877 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ C₄H₉ — 878 CH₃ CH₂ H CH₃ OCH₃Cl H C₃H₇ C₃H₇ — 879 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ C₂H₅ — 880 CH₃ CH₂ HCl CH₃ F H H 4-CH₃O—C₆H₄ — 881 CH₃ CH₂ H Cl CH₃ F H c-C₃H₅ c-C₃H₅130-131 882 CH₃ CH₂ H Cl CH₃ F H C₂H₅ c-C₃H₅ — 883 CH₃ CH₂ H Cl CH₃ F HCH₃ c-C₃H₅ — 884 CH₃ CH₂ H Cl CH₃ F H CH₃ C₃H₇ — 885 CH₃ CH₂ H Cl CH₃ FH CH₃ C₄H₉ — 886 CH₃ CH₂ H Cl CH₃ F H CH₃ C₅H₁₁ — 887 CH₃ CH₂ H Cl CH₃ FH C₂H₅ C₄H₉ — 888 CH₃ CH₂ H Cl CH₃ F H C₃H₇ C₃H₇ — 889 CH₃ CH₂ H Cl CH₃F H C₂H₅ C₂H₅ — 890 CH₃ CH₂ H Cl CF₃ Cl H H 4-CH₃O—C₆H₄ — 891 CH₃ CH₂ HCl CF₃ Cl H c-C₃H₅ c-C₃H₅ — 892 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ c-C₃H₅ — 893CH₃ CH₂ H Cl CF₃ Cl H CH₃ c-C₃H₅ — 894 CH₂ CH₂ H Cl CF₃ Cl H CH₃ C₃H₇ —895 CH₃ CH₂ H Cl CF₃ Cl H CH₃ C₄H₉ — 896 CH₃ CH₂ H Cl CF₃ Cl H CH₃ C₅H₁₁— 897 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ C₄H₉ — 898 CH₃ CH₂ H Cl CF₃ Cl H C₃H₇C₃H₇ — 899 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ C₂H₅ — 900 CH₃ CH₂ H CH₃ OCH₃ H HH C₄H₉ oil 901 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₂H₅ 69-73 902 CH₃ CH₂ H ClCH₃ H H C₃H₇ C₃H₇ oil 903 CH₃ CH₂ H Cl CF₃ F H H 4-CH₃O—C₆H₄ — 904 CH₃CH₂ H Cl CF₃ F H c-C₃H₅ c-C₃H₅ — 905 CH₃ CH₂ H Cl CF₃ F H C₂H₅ c-C₃H₅ —906 CH₃ CH₂ H Cl CF₃ F H CH₃ c-C₃H₅ — 907 CH₃ CH₂ H Cl CF₃ F H CH₃ C₃H₇— 908 CH₃ CH₂ H Cl CF₃ F H CH₃ C₄H₉ — 909 CH₃ CH₂ H Cl CF₃ F H CH₃ C₅H₁₁— 910 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₄H₉ — 911 CH₃ CH₂ H Cl CF₃ F H C₃H₇C₃H₇ — 912 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₂H₅ — 913 CH₃ CH₂ H Cl OCH₃ Cl H H4-CH₃O—C₆H₄ — 914 CH₃ CH₂ H Cl OCH₃ Cl H c-C₃H₅ c-C₃H₅ oil 915 CH₃ CH₂ HCl OCH₃ Cl H C₂H₅ c-C₃H₅ — 916 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ c-C₃H₅ — 917CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₃H₇ — 918 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₄H₉ —919 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₅H₁₁ — 920 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅C₄H₉ — 921 CH₃ CH₂ H Cl OCH₃ Cl H C₃H₇ C₃H₇ — 922 CH₃ CH₂ H Cl OCH₃ Cl HC₂H₅ C₂H₅ — 923 CH₃ CH₂ H Cl OCH₃ F H H 4-CH₃O—C₆H₄ — 924 CH₃ CH₂ H ClOCH₃ F H c-C₃H₅ c-C₃H₅ — 925 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ c-C₃H₅ — 926 CH₃CH₂ H Cl OCH₃ F H CH₃ c-C₃H₅ — 927 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₃H₇ — 928CH₃ CH₂ H Cl OCH₃ F H CH₃ C₄H₉ — 929 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₅H₁₁ —930 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₄H₉ — 931 CH₃ CH₂ H Cl OCH₃ F H C₃H₇C₃H₇ — 932 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₂H₅ — 933 CH₃ CH₂ H Cl OCH₃ CH₃ HH 4-CH₃O—C₆H₄ — 934 CH₃ CH₂ H Cl OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ 150-151 935CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ c-C₃H₅ — 936 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃c-C₃H₅ — 937 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ C₃H₇ — 938 CH₃ CH₂ H Cl OCH₃CH₃ H CH₃ C₄H₉ — 939 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ C₅H₁₁ — 940 CH₃ CH₂ HCl OCH₃ CH₃ H C₂H₅ C₄H₉ — 941 CH₃ CH₂ H Cl OCH₃ CH₃ H C₃H₇ C₃H₇ — 942CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ C₂H₅ — 943 CH₃ CH₂ H CH₃ OCH₃ CH₃ H H4-CH₃O—C₆H₄ — 944 CH₃ CH₂ H CH₃ OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ 148-151 945 CH₃CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ c-C₃H₅ oil 946 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃c-C₃H₅ — 947 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ C₃H₇ oil 948 CH₃ CH₂ H CH₃OCH₃ CH₃ H CH₃ C₄H₉ — 949 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ C₅H₁₁ — 950 CH₃CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ C₄H₉ — 951 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₃H₇ C₃H₇oil 952 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ C₂H₅ oil 953 CH₃ CH₂ H Cl H Cl H H4-CH₃O—C₆H₄ — 954 CH₃ CH₂ H Cl H Cl H c-C₃H₅ c-C₃H₅ 151-153 955 CH₃ CH₂H Cl H Cl H C₂H₅ c-C₃H₅ — 956 CH₃ CH₂ H Cl H Cl H CH₃ c-C₃H₅ — 957 CH₃CH₂ H Cl H Cl H CH₃ C₃H₇ — 958 CH₃ CH₂ H Cl H Cl H CH₃ C₄H₉ — 959 CH₃CH₂ H Cl H Cl H CH₃ C₅H₁₁ — 960 CH₃ CH₂ H Cl H Cl H C₂H₅ C₄H₉ — 961 CH₃CH₂ H Cl H Cl H C₃H₇ C₃H₇ — 962 CH₃ CH₂ H Cl H Cl H C₂H₅ C₂H₅ — 963 CH₃CH₂ H Cl Cl OCH₃ H H 4-CH₃O—C₆H₄ — 964 CH₃ CH₂ H Cl Cl OCH₃ H c-C₃H₅c-C₃H₅ — 965 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ c-C₃H₅ — 966 CH₃ CH₂ H Cl ClOCH₃ H CH₃ c-C₃H₅ — 967 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ C₃H₇ — 968 CH₃ CH₂ HCl Cl OCH₃ H CH₃ C₄H₉ — 969 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ C₄H₁₁ — 970 CH₃CH₂ H Cl Cl OCH₃ H C₂H₅ C₄H₉ — 971 CH₃ CH₂ H Cl Cl OCH₃ H C₃H₇ C₃H₇ —972 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ C₂H₅ — 973 CH₃ CH₂ H Cl CH₃ OCH₃ H H4-CH₃O—C₆H₄ — 974 CH₃ CH₂ H Cl CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 975 CH₃ CH₂ HCl CH₃ OCH₃ H C₂H₅ c-C₃H₅ — 976 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ c-C₃H₅ — 977CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₃H₇ — 978 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₄H₉— 979 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₅H₁₁ — 980 CH₃ CH₂ H Cl CH₃ OCH₃ HC₂H₅ C₄H₉ — 981 CH₃ CH₂ H Cl CH₃ OCH₃ H C₃H₇ C₃H₇ — 982 CH₃ CH₂ H Cl CH₃OCH₃ H C₂H₅ C₂H₅ — 983 CH₃ CH₂ H CH₃ Cl OCH₃ H H 4-CH₃O—C₆H₄ — 984 CH₃CH₂ H CH₃ Cl OCH₃ H c-C₃H₅ c-C₃H₅ — 985 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅c-C₃H₅ — 986 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₃ c-C₃H₅ — 987 CH₃ CH₂ H CH₃ ClOCH₃ H CH₃ C₃H₇ — 988 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₂ C₄H₉ — 989 CH₃ CH₂ HCH₃ Cl OCH₃ H CH₃ C₅H₁₁ — 990 CH₃ CH₃ H CH₃ Cl OCH₃ H C₂H₅ C₄H₉ — 991CH₃ CH₂ H CH₃ Cl OCH₃ H C₃H₇ C₃H₇ — 992 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅C₂H₅ — 993 CH₃ CH₂ H CH₃ CH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 994 CH₃ CH₂ H CH₃CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 995 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ c-C₃H₅ —996 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ c-C₃H₅ — 997 CH₃ CH₂ H CH₃ CH₃ OCH₃ HCH₃ C₃H₇ — 998 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ C₄H₉ — 999 CH₃ CH₂ H CH₃ CH₃OCH₃ H CH₃ C₅H₁₁ — 1000 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ C₄H₉ — 1001 CH₃CH₂ H CH₃ CH₃ OCH₃ H C₃H₇ C₃H₇ — 1002 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ C₂H₅— 1003 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H H 4-CH₃O—C₆H₄ oil 1004 CH₃ CH₂ H CH₃OCH₃ OCH₃ H c-C₃H₅ c-C₃H₅ 138-140 1005 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₂H₅c-C₃H₅ — 1006 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ c-C₃H₅ — 1007 CH₃ CH₂ H CH₃OCH₃ OCH₃ H CH₃ C₃H₇ — 1008 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₄H₉ — 1009CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1010 CH₃ CH₂ H CH₃ OCH₃ OCH₃ HC₂H₅ C₄H₉ — 1011 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₃H₇ C₃H₇ — 1012 CH₃ CH₂ HCH₃ OCH₃ OCH₃ H C₂H₅ C₂H₅ oil 1013 CH₃ CH₂ H Cl OCH₃ OCH₃ H H4-CH₃O—C₆H₄ — 1014 CH₃ CH₂ H Cl OCH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1015 CH₃ CH₂H Cl OCH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1016 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ c-C₃H₅— 1017 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ C₃H₇ — 1018 CH₃ CH₂ H Cl OCH₃ OCH₃ HCH₃ C₄H₉ — 1019 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1020 CH₃ CH₂ H ClOCH₃ OCH₃ H C₂H₅ C₄H₉ — 1021 CH₃ CH₂ H Cl OCH₃ OCH₃ H C₃H₇ C₃H₇ — 1022CH₃ CH₂ H Cl OCH₃ OCH₃ H C₂H₅ C₂H₅ — 1023 CH₃ CH₂ H Cl OCF₃ H H H4-CH₃O—C₆H₄ oil 1024 CH₃ CH₂ H Cl OCF₃ H H c-C₃H₅ c-C₃H₅ 119-120 1025CH₃ CH₂ H Cl OCF₃ H H C₂H₅ c-C₃H₅ 103-104 1026 CH₃ CH₂ H Cl OCF₃ H H CH₃c-C₃H₅ — 1027 CH₃ CH₂ H Cl OCF₃ H H CH₃ C₃H₇ oil 1028 CH₃ CH₂ H Cl OCF₃H H CH₃ C₄H₉ oil 1029 CH₃ CH₂ H Cl OCF₃ H H CH₃ C₅H₁₁ — 1030 CH₃ CH₂ HCl OCF₃ H H C₂H₅ C₄H₉ — 1031 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ C₃H₇ — 1032 CH₃CH₂ H Cl OCF₃ H H C₂H₅ C₂H₅ oil 1033 CH₃ CH₂ H Cl SCF₃ H H H 4-CH₃O—C₆H₄— 1034 CH₃ CH₂ H Cl SCF₃ H H c-C₃H₅ c-C₃H₅ — 1035 CH₃ CH₂ H Cl SCF₃ H HC₂H₅ c-C₃H₅ — 1036 CH₃ CH₂ H Cl SCF₃ H H CH₃ c-C₃H₅ — 1037 CH₃ CH₂ H ClSCF₃ H H CH₃ C₃H₇ — 1038 CH₃ CH₂ H Cl SCF₃ H H CH₃ C₄H₉ — 1039 CH₃ CH₂ HCl SCF₃ H H CH₃ C₅H₁₁ — 1040 CH₃ CH₂ H Cl SCF₃ H H C₂H₅ C₄H₉ — 1041 CH₃CH₂ H Cl SCF₃ H H C₃H₇ C₃H₇ — 1042 CH₃ CH₂ H Cl SCF₃ H H C₂H₅ C₂H₅ —1044 CH₃ CH₂ H Cl CF₃ H H H 4-CH₃O—C₆H₄ 105-107 1045 CH₃ CH₂ H CF₃ Q3 HH c-C₃H₅ c-C₃H₅ 168-169 1046 CH₃ CH₂ H Cl Q3 H H c-C₃H₅ c-C₃H₅ 130-1321047 CH₃ CH₂ H CF₃ SCH₃ H H c-C₃H₅ c-C₃H₅ — 1048 CH₃ CH₂ H Cl SCH₃ H Hc-C₃H₅ c-C₃H₅ — 1049 CH₃ CH₂ H CF₃ COCH₃ H H c-C₃H₅ c-C₃H₅ — 1050 CH₃CH₂ H Cl COCH₃ H H c-C₃H₅ c-C₃H₅ — 1051 CH₃ CH₂ H CF₃ CHCH₂ H H c-C₃H₅c-C₃H₅ — 1052 CH₃ CH₂ H Cl CHCH₂ H H c-C₃H₅ c-C₃H₅ — 1053 CH₃ CH₂ H ClCH₃ H H H 4-CH₃O—C₆H₄ 113-115 1054 CH₃ CH₂ H OCH₃ OCH₃ H H H 4-CH₃O—C₆H₄— 1055 CH₃ CH₂ H OCH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ 128-130 1056 CH₃ CH₂ H OCH₃OCH₃ H H C₂H₅ c-C₃H₅ — 1057 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ c-C₃H₅ — 1058CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₃H₇ — 1059 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₄H₉— 1060 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₅H₁₁ — 1061 CH₃ CH₂ H OCH₃ OCH₃ H HC₂H₅ C₄H₉ — 1062 CH₃ CH₂ H OCH₃ OCH₃ H H C₃H₇ C₃H₇ — 1063 CH₃ CH₂ H OCH₃OCH₃ H H C₂H₅ C₂H₅ — 1064 CH₃ CH₂ H OCH₃ CF₃ H H H 4-CH₃O—C₆H₄ — 1065CH₃ CH₂ H OCH₃ CF₃ H H c-C₃H₅ c-C₃H₅ 158-159 1066 CH₃ CH₂ H OCH₃ CF₃ H HC₂H₅ c-C₃H₅ — 1067 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ c-C₃H₅ — 1068 CH₃ CH₂ HOCH₃ CF₃ H H CH₃ C₃H₇ — 1069 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ C₄H₉ — 1070 CH₃CH₂ H OCH₃ CF₃ H H CH₃ C₅H₁₁ — 1071 CH₃ CH₂ H OCH₃ CF₃ H H C₂H₅ C₄H₉ —1072 CH₃ CH₂ H OCH₃ CF₃ H H C₃H₇ C₃H₇ — 1073 CH₃ CH₂ H OCH₃ CF₃ H H C₂H₅C₂H₅ — 1074 CH₃ CH₂ H CF₃ OCH₃ H H H 4-CH₃O—C₆H₄ oil 1075 CH₃ CH₂ H CF₃OCH₃ H H c-C₃H₅ c-C₃H₅ 129-130 1076 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ c-C₃H₅119-122 1077 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ c-C₃H₅ — 1078 CH₃ CH₂ H CF₃ OCH₃H H CH₃ C₃H₇ oil 1079 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ C₄H₉ oil 1080 CH₃ CH₂ HCF₃ OCH₃ H H CH₃ C₅H₁₁ — 1081 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ C₄H₉ — 1082CH₃ CH₂ H CF₃ OCH₃ H H C₃H₇ C₃H₇ oil 1083 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅C₂H₅ 77-78 1084 CH₃ CH₂ H OCH₃ Cl OCH₃ H H 4-CH₃O—C₆H₄ — 1085 CH₃ CH₂ HOCH₃ Cl OCH₃ H c-C₃H₅ c-C₃H₅ — 1086 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₂H₅ c-C₃H₅— 1087 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ c-C₃H₅ — 1088 CH₃ CH₂ H OCH₃ Cl OCH₃H CH₃ C₃H₇ — 1089 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ C₄H₉ — 1090 CH₃ CH₂ HOCH₃ Cl OCH₃ H CH₃ C₅H₁₁ — 1091 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₂H₅ C₄H₉ —1092 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₃H₇ C₃H₇ — 1093 CH₃ CH₂ H OCH₃ Cl OCH₃ HC₂H₅ C₂H₅ — 1094 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 1095 CH₃ CH₂H OCH₃ CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1096 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₂H₅c-C₃H₅ — 1097 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ c-C₃H₅ — 1098 CH₃ CH₂ H OCH₃CH₃ OCH₃ H CH₃ C₃H₇ — 1099 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ C₄H₉ — 1100 CH₃CH₂ H OCH₃ CH₃ OCH₃ H CH₃ C₅H₁₁ — 1101 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₂H₅C₄H₉ — 1102 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₃H₇ C₃H₇ — 1103 CH₃ CH₂ H OCH₃CH₃ OCH₃ H C₂H₅ C₂H₅ — 1104 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H H 4-CH₃O—C₆H₄ —1105 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1106 CH₃ CH₂ H OCH₃ CH₃OCH₃ H C₂H₅ c-C₃H₅ — 1107 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ c-C₃H₅ — 1108CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ C₃H₇ — 1109 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃C₄H₉ — 1110 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ C₅H₁₁ — 1111 CH₃ CH₂ H OCH₃CF₃ OCH₃ H C₂H₅ C₄H₉ — 1112 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₃H₇ C₃H₇ — 1113CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₂H₅ C₂H₅ — 1114 CH₃ CH₂ H OCH₃ CN OCH₃ H H4-CH₃O—C₆H₄ — 1115 CH₃ CH₂ H OCH₃ CN OCH₃ H c-C₃H₅ c-C₃H₅ — 1116 CH₃ CH₂H OCH₃ CN OCH₃ H C₂H₅ c-C₃H₅ — 1117 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ c-C₃H₅— 1118 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ C₃H₇ — 1119 CH₃ CH₂ H OCH₃ CN OCH₃ HCH₃ C₄H₉ — 1120 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ C₅H₁₁ — 1121 CH₃ CH₂ H OCH₃CN OCH₃ H C₂H₅ C₄H₉ — 1122 CH₃ CH₂ H OCH₃ CN OCH₃ H C₃H₇ C₃H₇ — 1123 CH₃CH₂ H OCH₃ CN OCH₃ H C₂H₅ C₂H₅ — 1124 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H H4-CH₃O—C₆H₄ — 1125 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1126 CH₃CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1127 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃c-C₃H₅ — 1128 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ C₃H₇ — 1129 CH₃ CH₂ H OCH₃OCH₃ OCH₃ H CH₃ C₄H₉ — 1130 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1131CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ C₄H₉ — 1132 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ HC₃H₇ C₃H₇ — 1133 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ C₂H₅ — 1134 CH₃ CH₂ HCH₃ CH₃ H CH₃ C₂H₅ CH₂OSO₂CH₃ 110-111 1135 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅CH₂SCH₃ 134-135 1136 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂Cl 140-141 1137 CH₃CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN 142-147 1138 CH₃ CH₂ H Cl Cl H H C₂H₅CH₂OSO₂CH₃ — 1139 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂SCH₃ — 1140 CH₃ CH₂ H ClCl H H C₂H₅ CH₂Cl — 1141 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂CN — 1142 CH₃ CH₂ HCl CF₃ H H C₂H₅ CH₂OSO₂CH₃ — 1143 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂SCH₃ —1144 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂Cl — 1145 CH₃ CH₂ H Cl CF₃ H H C₂H₅CH₂CN — 1146 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH₂OSO₂CH₃ — 1147 CH₃ CH₂ H ClOCH₃ H H C₂H₅ CH₂SCH₃ — 1148 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH₂Cl — 1149 CH₃CH₂ H Cl OCH₃ H H C₂H₅ CH₂CN — 1150 CH₃ CH₂ H CF₃ OCH₃ H H C₃H₇ c-C₃H₅oil 1151 CH₃ CH₂ H Cl CF₃ H H CH₃ C₃H₇ 97-98 1152 CH₃ CH₂ H CH₃ OCH₃ CH₃H C₆H₅ c-C₃H₅ — 1153 CH₃ CH₂ H Cl CF₃ H H C₆H₅ c-C₃H₅ oil 1154 CH₃ CH₂ HCl OCH₃ H H C₆H₅ c-C₃H₅ — 1155 CH₃ CH₂ H Cl OCF₃ H H C₆H₅ c-C₃H₅ oil1156 CH₃ CH₂ H Cl CH₃ H H C₆H₅ c-C₃H₅ 119-120 1157 CH₃ CH₂ H CF₃ OCH₃ HH C₆H₅ c-C₃H₅ oil 1158 CH₃ CH₂ H Cl Cl H CH₃ C₆H₅ c-C₃H₅ oil 1159 CH₃CH₂ H CH₃ OCH₃ Cl H C₆H₅ c-C₃H₅ — 1160 CH₃ CH₂ H CH₃ OCH₃ F H C₆H₅c-C₃H₅ — 1161 CH₃ CH₂ H Cl Cl H H 4-F—C₆H₄ c-C₃H₅ oil 1162 CH₃ CH₂ H CH₃OCH₃ CH₃ H 4-F—C₆H₄ c-C₃H₅ — 1163 CH₃ CH₂ H Cl CF₃ H H 4-F—C₆H₄ c-C₃H₅oil 1164 CH₃ CH₂ H Cl OCH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1165 CH₃ CH₂ H Cl OCF₃H H 4-F—C₆H₄ c-C₃H₅ — 1166 CH₃ CH₂ H Cl CH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1167CH₃ CH₂ H CF₃ OCH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1168 CH₃ CH₂ H Cl Cl H CH₃4-F—C₆H₄ c-C₃H₅ — 1169 CH₃ CH₂ H CH₃ OCH₃ Cl H 4-F—C₆H₄ c-C₃H₅ — 1170CH₃ CH₂ H CH₃ OCH₃ F H 4-F—C₆H₄ c-C₃H₅ — 1171 CH₃ CH₂ H Cl Cl H H CH₃c-C₄H₇ 109-110 1172 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ c-C₄H₇ — 1173 CH₃ CH₂ HCl CF₃ H H CH₃ c-C₄H₇ 136-137 1174 CH₃ CH₂ H Cl OCH₃ H H CH₃ c-C₄H₇ —1175 CH₃ CH₂ H Cl OCF₃ H H CH₃ c-C₄H₇ — 1176 CH₃ CH₂ H Cl CH₃ H H CH₃c-C₄H₇ — 1177 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ c-C₄H₇ — 1178 CH₃ CH₂ H Cl Cl HCH₃ CH₃ c-C₄H₇ — 1179 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ c-C₄H₇ — 1180 CH₃ CH₂H CH₃ OCH₃ F H CH₃ c-C₄H₇ — 1181 CH₃ CH₂ H Cl Cl H H C₂H₅ c-C₄H₇ — 1182CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ c-C₄H₇ — 1183 CH₃ CH₂ H Cl CF₃ H H C₂H₅c-C₄H₇ — 1184 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ c-C₄H₇ — 1185 CH₃ CH₂ H Cl OCF₃H H C₂H₅ c-C₄H₇ — 1186 CH₃ CH₂ H Cl CH₃ H H C₂H₅ c-C₄H₇ — 1187 CH₃ CH₂ HCF₃ OCH₃ H H C₂H₅ c-C₄H₇ — 1188 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ c-C₄H₇ — 1189CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ c-C₄H₇ — 1190 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅c-C₄H₇ — 1191 CH₃ CH₂ H Cl Cl H H C₃H₇ c-C₄H₇ — 1192 CH₃ CH₂ H CH₃ OCH₃CH₃ H C₃H₇ c-C₄H₇ — 1193 CH₃ CH₂ H Cl CF₃ H H C₃H₇ c-C₄H₇ — 1194 CH₃ CH₂H Cl OCH₃ H H C₃H₇ c-C₄H₇ — 1195 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ c-C₄H₇ —1196 CH₃ CH₂ H Cl CH₃ H H C₃H₇ c-C₄H₇ — 1197 CH₃ CH₂ H CF₃ OCH₃ H H C₃H₇c-C₄H₇ — 1198 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ c-C₄H₇ — 1199 CH₃ CH₂ H CH₃OCH₃ Cl H C₃H₇ c-C₄H₇ — 1200 CH₃ CH₂ H CH₃ OCH₃ F H C₃H₇ c-C₄H₇ — 1201CH₃ CH₂ H Cl Cl H H c-C₄H₇ c-C₄H₇ — 1202 CH₃ CH₂ H CH₃ OCH₃ CH₃ H c-C₄H₇c-C₄H₇ — 1203 CH₃ CH₂ H Cl CF₃ H H c-C₄H₇ c-C₄H₇ — 1204 CH₃ CH₂ H ClOCH₃ H H c-C₄H₇ c-C₄H₇ — 1205 CH₃ CH₂ H Cl OCF₃ H H c-C₄H₇ c-C₄H₇ — 1206CH₃ CH₂ H Cl CH₃ H H c-C₄H₇ c-C₄H₇ — 1207 CH₃ CH₂ H CF₃ OCH₃ H H c-C₄H₇c-C₄H₇ — 1208 CH₃ CH₂ H Cl Cl H CH₃ c-C₄H₇ c-C₄H₇ — 1209 CH₃ CH₂ H CH₃OCH₃ Cl H c-C₄H₇ c-C₄H₇ — 1210 CH₃ CH₂ H CH₃ OCH₃ F H c-C₄H₇ c-C₄H₇ —1211 CH₃ S H SCH₃ Cl H Cl C₂H₅ C₃H₇ 63-65 1212 CH₃ CH₂ H OCH₃ Cl H Hc-C₃H₅ c-C₃H₅ 152-154 1213 CH₃ CH₂ H OCH₃ Cl H H C₂H₅ c-C₃H₅ — 1214 CH₃CH₂ H OCH₃ Cl H H C₃H₇ c-C₃H₅ — 1215 CH₃ CH₂ H OCH₃ Cl H H CH₃ c-C₃H₇ —1216 CH₃ CH₂ H OCH₃ Cl H H CH₃ C₃H₇ — 1217 CH₃ CH₂ H OCH₃ Cl H H C₂H₅C₃H₇ — 1218 CH₃ CH₂ H OCH₃ Cl H H C₂H₅ C₂H₅ — 1219 CH₃ CH₂ H OCH₃ Cl H HC₃H₇ C₃H₇ — 1220 CH₃ CH₂ H OCH₃ Cl H H CH₃ C₄H₉ — 1221 CH₃ CH₂ H OCH₃ ClH H H 4-CH₃O—C₆H₄ — 1222 CH₃ CH₂ H OCH₃ CH₃ H H c-C₃H₅ c-C₃H₅ oil 1223CH₃ CH₂ H OCH₃ CH₃ H H C₂H₅ c-C₃H₅ — 1224 CH₃ CH₂ H OCH₃ CH₃ H H C₃H₇c-C₃H₅ — 1225 CH₃ CH₂ H OCH₃ CH₃ H H CH₃ c-C₄H₇ — 1226 CH₃ CH₂ H OCH₃CH₃ H H CH₃ C₃H₇ — 1227 CH₃ CH₂ H OCH₃ CH₃ H H C₂H₅ C₃H₇ — 1228 CH₃ CH₂H OCH₃ CH₃ H H C₂H₅ C₂H₅ — 1229 CH₃ CH₂ H OCH₃ CH₃ H H C₃H₇ C₃H₇ — 1230CH₃ CH₂ H OCH₃ CH₃ H H CH₃ C₄H₉ — 1231 CH₃ CH₂ H OCH₃ OCH₃ H H H4-CH₃O—C₆H₄ — 1232 CH₃ CH₂ H OCH₃ OCH₃ H F c-C₃H₅ c-C₃H₅ 176-178 1233CH₃ CH₂ H OCH₃ OCH₃ H F C₂H₅ c-C₃H₅ — 1234 CH₃ CH₂ H OCH₃ OCH₃ H F C₃H₇c-C₃H₅ — 1235 CH₃ CH₂ H OCH₃ OCH₃ H F CH₃ c-C₄H₇ — 1236 CH₃ CH₂ H OCH₃OCH₃ H F CH₃ C₃H₇ — 1237 CH₃ CH₂ H OCH₃ OCH₃ H F C₂H₅ C₃H₇ — 1238 CH₃CH₂ H OCH₃ OCH₃ H F C₂H₅ C₂H₅ — 1239 CH₃ CH₂ H OCH₃ OCH₃ H F C₃H₇ C₃H₇ —1240 CH₃ CH₂ H OCH₃ OCH₃ H F CH₃ C₄H₉ — 1241 CH₃ CH₂ H OCH₃ OCH₃ H F H4-CH₃O—C₆H₄ — 1242 CH₃ CH₂ H CF₃ F H H c-C₃H₅ c-C₃H₅ — 1243 CH₃ CH₂ HCF₃ F H H C₂H₅ c-C₃H₅ — 1244 CH₃ CH₂ H CF₃ F H H C₃H₇ c-C₃H₅ 115-1181245 CH₃ CH₂ H CF₃ F H H CH₃ c-C₄H₇ — 1246 CH₃ CH₂ H CF₃ F H H CH₃ C₃H₇— 1247 CH₃ CH₂ H CF₃ F H H C₂H₅ C₃H₇ — 1248 CH₃ CH₂ H CF₃ F H H C₂H₅C₂H₅ — 1249 CH₃ CH₂ H CF₃ F H H C₃H₇ C₃H₉ — 1250 CH₃ CH₂ H CF₃ F H H CH₃C₄H₉ — 1251 CH₃ CH₂ H CF₃ F H H H 4-CH₃O—C₆H₄ 57-70 1252 CH₃ CH₂ H CF₃ FH H BnOCH₂ BnOCH₂ oil 1253 CH₃ CH₂ H CF₃ F H H CH₃ C₆H₅ 119-120 1254 CH₃CH₂ H CF₃ F H H C₆H₅ C₆H₅ 135-139 1255 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ c-C₃H₅oil 1256 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ C₃H₇ oil 1257 CH₃ CH₂ H Cl CF₃ H H HCH₂═CH—CH═CH 83-85 1258 CH₃ CH₂ H CF₃ OBn H H c-C₃H₅ c-C₃H₅ 163-165 1259CH₃ CH₂ H CF₃ OH H H c-C₃H₅ c-C₃H₅ 245-246 1260 CH₃ CH₂ H CF₃ OC₃H₇ H Hc-C₃H₅ c-C₃H₅ 127-128 1261 CH₃ CH₂ H CF₃ OC₃H₇ H H C₂H₅ c-C₃H₅ — 1262CH₃ CH₂ H CF₃ OC₃H₇ H H C₃H₇ c-C₃H₅ — 1263 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃c-C₄H₇ — 1264 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃ C₃H₇ — 1265 CH₃ CH₂ H CF₃OC₃H₇ H H C₂H₅ C₃H₇ — 1266 CH₃ CH₂ H CF₃ OC₃H₇ H H C₂H₅ C₂H₅ — 1267 CH₃CH₂ H CF₃ OC₃H₇ H H C₃H₇ C₃H₇ — 1268 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃ C₄H₉ —1269 CH₃ CH₂ H CF₃ OC₃H₇ H H H 4-CH₃O—C₆H₄ — 1284 CH₃ CH₂ H CH₃ OH F Hc-C₃H₅ c-C₃H₅ — 1285 CH₃ CH₂ H CH₃ OH F H C₂H₅ c-C₃H₅ — 1286 CH₃ CH₂ HCH₃ OH F H C₃H₇ c-C₃H₅ — 1287 CH₃ CH₂ H CH₃ OH F H CH₃ c-C₄H₇ — 1288 CH₃CH₂ H CH₃ OH F H CH₃ C₃H₇ — 1289 CH₃ CH₂ H CH₃ OH F H C₂H₅ C₃H₇ — 1290CH₃ CH₂ H CH₃ OH F H C₂H₅ C₂H₅ — 1291 CH₃ CH₂ H CH₃ OH F H C₃H₇ C₃H₇ —1292 CH₃ CH₂ H CH₃ OH F H CH₃ C₄H₉ — 1293 CH₃ CH₂ H CH₃ OH F H H4-CH₃O—C₆H₄ — 1294 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ CH₃ 101-102 1295 CH₃CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₃H₅ oil 1296 CH₃ CH₂ H Cl Cl H H C₂H₅4-CH₃O—C₆H₄ oil 1297 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ C₂H₅ 133-135 1298 CH₃CH₂ H Cl Cl H CH₃ C₂H₅ C₃H₇ 123-125 1299 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ C₃H₇125-127 1300 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ c-C₃H₅ 157-159 1301 CH₃ O H CH₃OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ — 1302 CH₃ O H Cl CF₃ H H c-C₃H₅ c-C₃H₅ 149-1501303 CH₃ O H Cl OCH₃ H H c-C₃H₅ c-C₃H₅ 124-125 1304 CH₃ O H Cl COF₃ H Hc-C₃H₅ c-C₃H₅ — 1305 CH₃ O H Cl CH₃ H H c-C₃H₅ c-C₃H₅ — 1306 CH₃ O H CF₃OCH₃ H H c-C₃H₅ c-C₃H₅ — 1307 CH₃ O H Cl Cl H CH₃ c-C₃H₅ c-C₃H₅ — 1308CH₃ O H CH₃ OCH₃ Cl H c-C₃H₅ c-C₃H₅ — 1309 CH₃ O H CH₃ OCH₃ F H c-C₃H₅c-C₃H₅ — 1310 CH₃ O H CH₃ OCH₃ CH₃ H CH₃ C₃H₇ — 1311 CH₃ O H Cl CF₃ H HCH₃ C₃H₇ — 1312 CH₃ O H Cl OCH₃ H H CH₃ C₃H₇ — 1313 CH₃ O H Cl OCF₃ H HCH₃ C₃H₇ — 1314 CH₃ O H Cl CH₃ H H CH₃ C₃H₇ — 1315 CH₃ O H CF₃ OCH₃ H HCH₃ C₃H₇ — 1316 CH₃ O H Cl Cl H CH₃ CH₃ C₃H₇ — 1317 CH₃ O H CH₃ OCH₃ ClH CH₃ C₃H₇ — 1318 CH₃ O H CH₃ OCH₃ F H CH₃ C₃H₇ — 1319 CH₃ CH₂ H Cl Cl HH C₆H₅ C₆H₅ oil 1320 CH₃ CH₂ H Cl Cl H H C₆H₅ CH₃ oil 1321 CH₃ CH₂ H ClCl H H c-C₃H₅ 2-CH₃—C₆H₄ oil 1322 CH₃ CH₂ H Cl Cl H H C₄H₉ CH(CH₂OH)₂oil 1323 CH₃ CH₂ H Cl Cl H H C₆H₅ CO₂C₂H₅ oil 1324 CH₃ CH₂ H Cl Cl H HC₆H₅ CO₂H oil 1325 CH₃ CH₂ H Cl Cl H H C₆H₅ CH₂OH oil 1326 CH₃ CH₂ H CH₃OCH₃ Cl H H 2-Cl—C₆H₄ oil 1327 CH₃ CH₂ H CH₃ OCH₃ Cl H H 3-Cl—C₆H₄ oil1328 CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-Cl—C₆H₄ oil 1329 CH₃ CH₂ H CH₃ OCH₃ ClH H 3-CH₃O—C₆H₄ oil 1330 CH₃ CH₂ H CH₃ OCH₃ Cl H H 3-CN—C₆H₄ oil 1331CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-CN—C₆H₄ oil 1332 CH₃ CH₂ H CH₃ OCH₃ Cl H H4-BnO—C₆H₄ oil 1333 CH₃ CH₂ H CH₃ OCH₃ Cl H H 2,5-(CH₃O)— oil C₆H₃ 1334CH₃ CH₂ H CH₃ OCH₃ Cl H H 2-CH₃O—C₆H₄ oil 1335 CH₃ CH₂ H Cl Cl H H CNc-C₃H₅ oil 1336 CH₃ CH₂ H Cl Cl H H CH₃ CH₂OC₂H₅ 96-97 1337 CH₃ CH₂ H ClCl H H H CH(OH)CH₂OC₆H₅ oil 1338 CH₃ CH₂ H Cl Cl H H H CH(OH)CH₂C₆H₅ oil1339 CH₃ CH₂ H Cl Cl H H H CH(OH)C₃H₇ oil 1340 CH₃ CH₂ H Cl Cl H HCH(CH₃)₂ C(O)-1- 154-155 morpholinyl 1341 CH₃ CH₂ H Cl Cl H H C₂H₅CO₂CH₃ oil 1342 CH₃ CH₂ H Cl Cl H H CH₃ CO₂CH₃ oil 1343 CH₃ CH₂ H Cl ClH H CH₃ CH oil 1344 CH₃ CH₂ H Cl Cl H H CH₃ COCH₃ oil 1345 CH₃ CH₂ H ClCl H H H 2-Cl—C₆H₄ 149-152 1346 CH₃ CH₂ H Cl Cl H H H 3-Cl—C₆H₄ oil 1347CH₃ CH₂ H Cl Cl H H H 4-F—C₆H₄ 148-149 1348 CH₃ CH₂ H Cl Cl H H H4-CN—C₆H₄ 199-200 1349 CH₃ CH₂ H Cl Cl H H H 4-Cl—C₆H₄ 183-184 1350 CH₃CH₂ H Cl Cl H H c-C₃H₅ c-C₄H₇ — 1351 CH₃ CH₂ H CH₃ OCH₃ CH₃ H c-C₃H₅c-C₄H₇ — 1352 CH₃ CH₂ H Cl CF₃ H H c-C₃H₅ c-C₄H₇ — 1353 CH₃ CH₂ H ClOCH₃ H H c-C₃H₅ c-C₄H₇ — 1354 CH₃ CH₂ H Cl OCF₃ H H c-C₃H₅ c-C₄H₇ — 1355CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ c-C₄H₇ — 1356 CH₃ CH₂ H CF₃ OCH₃ H H c-C₃H₅c-C₄H₇ — 1357 CH₃ CH₂ H Cl Cl H CH₃ c-C₃H₅ c-C₄H₇ — 1358 CH₃ CH₂ H CH₃OCH₃ Cl H c-C₃H₅ c-C₄H₇ — 1359 CH₃ CH₂ H CH₃ OCH₃ F H c-C₃H₅ c-C₄H₇ —1360 CH₃ CH₂ H Cl OCH₃ F H c-C₃H₅ c-C₃H₅ — 1361 CH₃ CH₂ H Cl OCH₃ F HC₂H₅ c-C₃H₅ — 1362 CH₃ CH₂ H Cl OCH₃ F H C₃H₇ c-C₃H₅ — 1363 CH₃ CH₂ H ClOCH₃ F H CH₃ c-C₄H₇ — 1364 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₃H₇ — 1365 CH₃ CH₂H Cl OCH₃ F H C₂H₅ C₃H₇ — 1366 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₂H₅ — 1367CH₃ CH₂ H Cl OCH₃ F H C₃H₇ C₃H₇ — 1368 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₄H₉ —1369 CH₃ CH₂ H Cl OCH₃ F H H 4-CH₃O—C₆H₄ — 1370 CH₃ CH₂ H CF₃ OCH₃ H HC₂H₅ C₃H₇ oil 1371 CH₃ CH₂ H Cl Cl H H CH₃ 2-CH₃-c-C₃H₄ oil 1372 CH₃ CH₂H CH₃ OCH₃ CH₃ H CH₃ 2-CH₃-c-C₃H₄ — 1373 CH₃ CH₂ H Cl CF₃ H H CH₃2-CH₃-c-C₃H₄ — 1374 CH₃ CH₂ H Cl OCH₃ H H CH₃ 2-CH₃-c-C₃H₄ — 1375 CH₃CH₂ H Cl OCF₃ H H CH₃ 2-CH₃-c-C₃H₄ — 1376 CH₃ CH₂ H Cl CH H H CH₃2-CH₃-c-C₃H₄ — 1377 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ 2-CH₃-c-C₃H₄ — 1378 CH₃CH₂ H Cl Cl H CH₃ CH₃ 2-CH₃-c-C₃H₄ — 1379 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃2-CH₃-c-C₃H₄ — 1380 CH₃ O H Cl Cl H H CH₃ 2-CH₃-c-C₃H₄ — 1381 CH₃ CH₂ HCl Cl H H CH₃ 2-C₆H₅-c-C₃H₄ — 1382 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃2-C₆H₅-c-C₃H₄ — 1383 CH₃ CH₂ H Cl CF₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1384 CH₃CH₂ H Cl OCH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1385 CH₃ CH₂ H Cl OCF₃ H H CH₃2-C₆H₅-c-C₃H₄ — 1386 CH₃ CH₂ H Cl CH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1387 CH₃CH₂ H CF₃ OCH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1388 CH₃ CH₂ H Cl Cl H CH₃ CH₃2-C₆H₅-c-C₃H₄ — 1389 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ 2-C₆H₅-c-C₃H₄ — 1390CH₃ O H Cl Cl H H CH₃ 2-C₆H₅-c-C₃H₄ — 1391 CH₃ CH₂ H Cl Cl H H CH₃ 2-(2-— pyridyl)-c-C₃H₄ 1392 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ 2-(2- —pyridyl)-c-C₃H₄ 1393 CH₃ CH₂ H Cl CF₃ H H CH₃ 2-(2- — pyridyl)-c-C₃H₄1394 CH₃ CH₂ H Cl OCH₃ H H CH₃ 2-(2- — pyridyl)-c-C₃H₄ 1395 CH₃ CH₂ H ClOCF₃ H H CH₃ 2-(2- — pyridyl)-c-C₃H₄ 1396 CH₃ CH₂ H Cl CH₃ H H CH₃ 2-(2-— pyridyl)-c-C₃H₄ 1397 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ 2-(2- —pyridyl)-c-C₃H₄ 1398 CH₃ CH₂ H Cl Cl H CH₃ CH₃ 2-(2- — pyridyl)-c-C₃H₄1399 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ 2-(2- — pyridyl)-c-C₃H₄ 1400 CH₃ O H ClCl H H CH₃ 2-(2- — pyridyl)-c-C₃H₄ Key: ^(a)Where the compound isindicated as an “oil”, data is provided below: Example 3 spectral data:TLC R_(f) 0.27(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.90(1H, s), 6.95(2H, s), 4.45(1H, br), 4.27-4.17(2H, m), 3.85(1H, dd,J=9.5, 4.8Hz), 3.27(3H, s), 2.94(2H, q, J=7.5Hz), 2.56-2.46(1H, m),2.32(3H, s), 2.06(3H, s), 2.03(3H, s), 1.37(3H, t, J=7.5Hz), 0.85(3H, t,J=7.5Hz). MS(NH₃—CI): m/e 355(3), 354(25), 353(100). Analysis calc'd forC₂₁H₂₈N₄O.1.5H₂O: C, 66.46; # H, 8.23; N, 14.76; found: C, 67.00; H,8.10; N, 14.38. Example 8 spectral data: TLC R_(f) 0.34(50:50 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.89(1H, s), 6.95(2H, s),4.46(1H, br), 3.41-3.33(1H, m), 3.22(3H, s), 2.94(2H, q, J=7.3Hz),2.93-2.85(1H, m), 2.84-2.69(2H, m), 2.51(1H, br), 2.32(3H, s),2.30-2.20(1H, m), 2.04(6H, s), 1.37(3H, t, J=7.7Hz), 0.84(3H, t,J=7.3Hz). MS(NH₃—CI): m/e calc'd for C₂₂H₃₀N₄O: 366.2420, found366.2400; 369(3), 368(27), 367(100). Example 10 spectral data: TLC R_(F)0.13(ethyl acetate). ¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 8.10(3H, s),7.96(1H, s), 6.96(2H, s), 4.39(1H, br), 4.24-4.14(1H, m), 4.12-4.00(1H,m), 3.20(1H, br), 2.80(2H, q, J=7.0Hz), 2.78-2.68(1H, m), 2.42(1H, br),2.33(3H, s), 2.13-2.04(1H, m), 2.06(3H, s), 2.03(3H, s), 1.33(3H, t,J=7.5Hz), 0.80(3H, t, J=7.3Hz). MS(NH₃—CI): m/e calc'd for C₂₃H₃₀N₇:404.2563, found 404.2556; # 406(4), 405(28), 404(100). Example 11spectral data: TLC R_(F) 0.60(ethyl acetate). ¹H NMR(300MHz, CDCl₃):δ8.92(1H, s), 8.51(1H, s), 6.96(2H, s), 4.78-4.68(1H, m), 4.57-4.47(1H,m), 4.32-4.22(1H, m), 3.43(1H, br), 2.81(2H, q, J=6.9Hz), 2.78(1H, br),2.43(1H, br), 2.33(3H, s), 2.10-2.00(1H, m), 2.07(3H, s), 2.03(3H, s),1.32(3H, t, J=7.0Hz), 0.78(3H, t, J=7.5Hz). MS(NH₃—CI: m/e calc'd forC₂₂H₂₉N₉: 405.2515, found 405.2509; 407(4), 406(27), 405(100). Example18 spectral data: TLC R_(F) 0.20(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ9.00(1H, s), 7.26(1H, obscurred), 6.96(2H, s),6.86-6.76(3H, m), 5.46(2H, s), 3.76(3H, s), 2.85(2H, q, J=7.7Hz),2.33(3H, s), 2.06(6H, s), 1.28(3H, t, J=7.7Hz). MS(NH₃—CI): m/e 389(4),388(28), 387(100). Analysis calc'd for C₂₄H₂₆N₄O: C, 74.58; H, 6.78; N,14.50; found: C, 74.36; H, 6.73; N, 13.83. Example 27 spectral data: TLCR_(F) 0.20(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H,s), 6.95(2H, s), 4.25(2H, t, J=7.5Hz), 2.93(2H, q, J=7.7Hz), 2.32(3H,s), 2.04(6H, s), 1.91-1.86(2H, m), 1.50-1.38(2H, m), 1.39(3H, t,J=7.7Hz), 1.01(3H, t, J=7.5Hz). MS(NH₃—CI): m/e 325(3), 324(23),323(100). Example 28 spectral data: TLC R_(F) 0.28(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H, s), 6.95(2H, s),4.24(2H, t, J=7.9Hz), 2.93(2H, q, J=7.6Hz), 2.32(3H, s), 2.04(6H, s),1.90(2H, m), 1.44-1.36(7H, m), 0.93(3H, t, J=7.1Hz). MS(NH₃—CI): m/e339(3), 338(25), 337(100). Analysis calc'd for C₂₁H₂₈N₄: C, 74.96; H,8.40; N, 16.65; found: C, 74.24; H, 8.22; N, 16.25. Example 34 spectraldata: MS(ESI): m/e 365(M+2), 363(M+H⁻, 100%). Example 35 spectral data:TLC R_(F) 0.31(20:80 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.94(1H, s), 7.71(1H, d, J=8.4Hz), 7.58(1H, d, J=1.8Hz), 7.41(1H, dd,J=8.4, 1.8Hz), 4.27(1H, br), 2.95(2H, q, J=7.3Hz), 2.41(2H, br),2.11-1.98(2H, br), 1.42(3H, t, J=7.3Hz), 1.37-1.20(3H, m), 1.09-0.99(1H,m), 0.84(3H, t, J=7.7Hz), 0.82(3H, t, J=7.7Hz). MS(NH₃—CI): m/e calc'dfor C₂₀H₂₅N₄Cl₂: 391.1456, # found 391.1458; 395(11), 394(14), 393(71),392(29), 391(100). Example 38 spectral data: MS(NH₃—CI): m/e 375(M+H⁺,100%). Example 40 spectral data: MS(NH₃—CI): m/e 377(M+H⁺, 100%).Example 48 spectral data: MS(NH₃—CI): m/e 423(M+H⁺, 100%). Example 50spectral data: TLC R_(F) 0.27(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ9.03(1H, s), 7.70(1H, d, J=8.0Hz), 7.59(1H, d,J=1.8Hz), 7.41(1H, dd, J=8.0, 1.8Hz), 7.36-7.30(2H, m), 7.24-7.19(3H,m), 5.50(2H, s), 2.87(2H, q, J=7.5Hz), 1.31(3H, t, J=7.5Hz). MS(NH₃—CI):m/e calc'd for C₂₀H₁₆N₄Cl₂: 382.0752, found 382.0746; 388(3), 387(12),386(16), 385(66), 384(26), 383(100). Example 51 spectral data:MS(NH₃—CI): m/e 413(M+H⁺, 100%). Example 54 spectral data: MS(NH₃—CI):m/e 459(M+H⁺, 100%). Example 68 spectral data: TLC R_(F) 0.28(30:70ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H, s), 6.69(2H, s),4.30-4.19(1H, m), 3.82(3H, s), 2.92(2H, q, J=7.6Hz), 2.41(1H, br),2.08(3H, s), 2.07(3H, s), 2.06(1H, br), 1.38(3H, t, J=7.6Hz),1.36-1.22(4H, m), 1.10-0.98(1H, m), 0.96-0.87(1H, m), 0.84(3H, t,J=7.0Hz), 0.81(3H, t, J=6.7Hz). MS(NH₃—CI): m/e 383(4), 382(27),381(100). Example 122 spectral data: TLC R_(F) 0.10(20:80 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.97(1H, s), 6.94(2H, s),4.14(2H, d, J=7.7Hz), 3.48(1H, q, J=7.0Hz), 2.63(3H, s), 2.31(3H, s),2.01(6H, s), 1.43-1.19(8H, m), 0.94(3H, t, J=7.3Hz), 0.84(3H, t,J=7.0Hz). MS(NH₃—CI): m/e 367(3), 366(25), 365(100). Example 123spectral data: TLC R_(F) 0.24(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.97(1H, s), 6.94(2H, s), 4.25(2H, t, J=8.1Hz),3.48(1H, q, J=7.1Hz), 2.63(3H, s), 2.31(3H, s), 2.01(6H, s), 1.81(2H,m), 1.47-1.19(8H, m), 0.91(6H, m). MS(NH₃—CI): m/e 381(4), 380(27),379(100). Analysis calc'd for C₂₄H₁₄N₄: C, 76.15; H, 9.05; N, 14.80;found: C, 76.29; H, 9.09; N, 14.75. Example 202 spectral data: TLC RF0.20(10:90 ethyl acetate-hexane). 1H NMR(300MHz, CDCl₃): d8.82(1H, s),6.96(2H, s), 4.46-4.38(1H, m), 4.13(3H, s), 2.34(3H, s), 2.28-2.11(2H,m), 2.07(6H, s), 1.95-1.81(2H, m), 1.38-1.17(3H, m), 1.14-0.99(1H, m),0.83(3H, t, J=7.7Hz), 0.80(3H, t, J=7.7Hz). MS(NH3—CI): m/e calc'd forC₂₂H₃₀N₄O: 366.2420, found 366.2408; 369(4), 368(26), 367(100). Example404 spectral data: TLC R_(F) 0.20(20:80 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ6.93(2H, s), 4.20(2H, t, J=7.7Hz), 2.90(2H, q,J=7.6Hz), 2.83(3H, s), 2.30(3H, s), 2.03(6H, s), 1.88(2H, m),1.42-1.34(7H, m), 0.93(3H, t, J=6Hz). MS(NH₃—Cl): m/e 353(3), 352(27),351(100). Example 414 spectral data: TLC R_(F) 0.36(20:80 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.92(1H, s), 7.66(1H, d,J=8.1Hz), 7.32-7.26(2H, m), 4.54(1H, m), 2.95(2H, q, J=7.4Hz), 2.43(3H,s), 2.39(1H, m), 2.03(1H, m), 1.74(3H, d, J=7.0Hz), 1.41(3H, t,J=7.5Hz), 1.31(1H, m), 1.16(1H, m), 0.92(3H, t, J=7.3Hz). MS(NH₃—CI):m/e calc'd for C₁₉H₂₄N₄Cl: 343.1690, found 343.1704; 346(7), 345(34),344(23), 343(100). Example 415 spectral data: TLC R_(F) 0.25(10:90 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H, s), 7.71(1H, d,J=8.1Hz), 7.34-7.30(2H, m), 4.30-4.20(1H, m), 2.94(2H, q, J=7.5Hz),2.50-2.35(2H, m), 2.44(3H, s), 2.08-1.95(2H, m), 1.43(3H, t, J=7.5Hz),1.29(3H, m), 1.08-0.98(1H, m), 0.84(3H, t, J=7.0Hz), 0.81(3H, t,J=7.3Hz). MS(NH₃—CI): m/e 374(7), 373(33), 372(25), 371(100). Analysiscalc'd for # C₂₁H₂₇ClN₄: C, 68.00; H, 7.35; N, 15.10; found: C, 68.25;H, 7.30; N, 14.85. Example 424 spectral data: TLC R_(F) 0.28(5:95 ethylacetate-dichloromethane). ¹H NMR(300MHz, CDCl₃): δ8.95(1H, s), 7.60(1H,d, J=7.7Hz), 7.37(1H, d, J=0.8Hz), 7.21(1H, dd, J=7.7, 0.8Hz),4.58-4.50(1H, m), 2.96(2H, dq, J=7.5, 2.0Hz), 2.46-2.33(1H, m), 2.40(3H,s) 2.08-1.96(1H, m), 1.74(3H, d, J=6.6Hz), 1.40(3H, t, J=7.5Hz),1.39-1.22(1H, m), 1.20-1.08(1H, m), 0.92(3H, t, J=7.3Hz). MS(NH₃—CI):m/e calc'd for # C₁₉H₂₄ClN₄: 343.1690, found 343.1697; 346(8), 345(38),344(25), 343(100). Example 434 spectral data: TLC R_(F) 0.78(50:50 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 6.95(2H, s),2.97(2H, J=7.3Hz), 2.60-2.50(1H, m), 2.41-2.33(1H, m), 2.32(3H, s),2.20-2.10(1H, m), 2.05(3H, s), 2.02(3H, s), 1.85-1.80(1H, m), 1.39(3H,t, J=7.5Hz), 0.85(3H, t, J=7.5Hz), 0.50-0.35(2H, m), 0.25-0.15(1H, m),0.10-0.00(1H, m). MS(NH₃—CI): m/e calc'd for C₂₃H₃₀N₄: # 362.2470, found362.2458; 365(4), 364(27), 363(100). Example 436 spectral data: TLCR_(F) 0.31(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.88(1H,s), 7.77(1H, d, J=9.2Hz), 6.87(2H, m), 4.40-4.25(1H, m), 3.86(3H, s),2.99(2H, q, J=7.5Hz), 2.60-2.35(2H, m), 2.47(3H, s), 2.15-2.00(1H, m),1.80-1.70(1H, m), 1.45(3H, t, J=7.5Hz), 0.84(3H, t, J=7.5Hz),0.50-0.35(2H, m), 0.30-0.20(1H, m), 0.10-0.00(1H, m), −0.85-−0.95(1H,m). Example 437 spectral data: TLC R_(F) 0.25(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 7.73(1H, d,J=9.2Hz), 6.89-6.86(2H, m), 4.58-4.51(1H, m), 3.86(3H, s), 2.95(2H, dq,J=7.6, 1.8Hz), 2.47(3H, s), 2.45-2.34(1H, m), 2.07-1.97(1H, m), 1.73(3H,d, J=7.0Hz), 1.42(3H, t, J=7.6Hz), 1.40-1.27(1H, m), 1.20-1.07(1H, m),0.92(3H, t, J=7.4Hz). MS(NH₃—CI): m/e calc'd for C₂₀H₂₇N₄O: # 339.2185,found 339.2187; 341(3), 340(22), 339(100). Analysis calc'd forC₂₀H₂₆N₄O: C, 70.98; H, 7.74; N, 16.55; found: C, 69.97; H, 7.48; N,15.84. Example 438 spectral data: TLC R_(F) 0.42(40:60 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.98(1H, s), 7.77(1H, d,J=9.1Hz), 7.17(2H, d, J=8.8Hz), 6.90-6.83(4H, m), 5.42(2H, s), 3.86(3H,s), 3.78(3H, s), 2.86(2H, q, J=7.5Hz), 2.49(3H, s), 1.33(3H, t,J=7.5Hz). MS(NH₃—CI): m/e 391(4), 390(26), 389(100). Analysis calc'd forC₂₃H₂₄N₄O₂: C, 71.11; H, 6.24; N, 14.42; found: C, 71.14; H, 5.97; H,14.03. Example 439 spectral data: TLC R_(F) 0.41(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.89(1H, s), 7.77(1H, d,J=3.1Hz), 6.89(2H, m), 3.86(3H, s), 3.53(1H, m), 2.91(2H, q, J=7.5Hz),2.49(3H, s), 2.28(1H, m), 2.21(1H, m), 1.43(3H, t, J=7.3Hz), 0.86(3H, t,J=7.3Hz), 0.78(2H, m), 0.46(2H, m), 0.20(1H, m). Example 440 spectraldata: TLC R_(F) 0.28(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.89(1H, s), 7.73(1H, d, J=9.1Hz), 6.90-6.86(2H, m), 4.60-4.40(1H, m),3.86(3H, s), 2.95(2H, dq, J=7.7, 2.2Hz), 2.47(3H, s), 2.44-2.36(1H, m),2.05-1.98(1H, m), 1.74(3H, d, J=7.0Hz), 1.42(3H, t, J=7.5Hz),1.40-1.20(5H, m), 1.13-1.05(1H, m), 0.830(3H, t, J=6.6Hz). Example 502spectral data: TLC R_(F) 0.63(50:50 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.92(1H, s), 6.95(2H, s), 4.60-4.47(1H, m),2.93(2H, q, J=7.7Hz), 2.43-2.33(1H, m), 2.32(3H, s), 2.16-2.06(1H, m),2.05(3H, s), 2.03(3H, s), 1.76(3H, d, J=7.0Hz), 1.36(3H, t, J=7.7Hz),1.36-1.20(4H, m), 0.86(3H, t, J=7.2Hz). MS(NH₃—CI): m/e calc'd forC₂₂H₃₀N₄: 350.2470, found 350.2480; 353(3), 352(28), # 351(100). Example503 spectral data: ¹H NMR(300MHz, CDCl₃): δ8.92(1H, s), 6.94(2H, s),4.58-4.48(1H, m), 2.93(2H, q, J=7.3Hz), 2.32(3H, s), 2.05(3H, s),2.02(3H, s), 1.76(3H, d, J=6.6Hz), 1.36(3H, t, J=7.3Hz), 1.34-1.05(8H,m), 0.88(3H, t, J=7Hz). MS(NH₃—CI): m/e calc'd for C₂₃H₃₂N₄: 365.2705,found 365.2685; 367(3), 366(27), 365(100). Example 506 spectral data:TLC R_(F) 0.28(20:80 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.95(1H, s), 7.67(1H, d, J=8.4Hz), 7.57(1H, d, =1.8Hz), 7.42-7.37(1H,m), 4.56(1H, hextet, J=7.1Hz), 2.99(2H, q, J=7.5Hz), 2.43-2.33(1H, m),2.09-1.97(1H, m), 1.74(3H, d, J=7.0Hz), 1.41(3H, t, J=7.5Hz),1.35-1.07(2H, m), 0.92(3H, t, J=7.3Hz), MS(NH₃—CI): m/e 367(12),366(14), 365(67), 364(24), 363(100). Example 507 spectral data:MS(NH₃—CI): m/e 377(M+H⁺, 100%). Example 511 spectral data: TLC R_(F)0.51(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.97(1H, s),7.87(1H, d, J=8.1Hz), 7.83(1H, d, =1.1Hz), 7.68(1H, dd, J=8.1, 1.1Hz),3.60-3.51(1H, m), 2.94(2H, q, J=7.5Hz), 2.53-2.39(1H, m), 2.36-2.20(1H,m), 1.96(1H, br), 1.42(3H, t, J=7.5Hz), 0.88(3H, t, J=7.3Hz),0.88-0.78(1H, m), 0.52-0.44(2H, m), 0.24-0.16(1H, m), MS(NH₃—CI): m/e412(7), # 411(33), 410(23), 409(100). Example 513 spectral data: TLCR_(F) 0.62(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.97(1H,s), 7.87(1H, d, J=8.0Hz), 7.83(1H, d, J=0.7Hz), 7.68(1H, dd, J=8.0,0.7Hz), 4.21(1H, br), 2.96(2H, q, J=7.5Hz), 2.42(2H, br), 2.12-1.97(2H,m), 1.43(3H, t, J=7.5Hz), 1.40-1.20(4H, m), 0.85(3H, t, J=7.3Hz),0.83(3H, t, J=7.6Hz). MS(NH₃—CI): m/e 428(8), 427(38), 426(29),425(100). Example 514 spectral data: TLC R_(F) 0.50(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H, s), 7.86(1H, d,J=8.1Hz), 7.83(1H, d, J=0.8Hz), 7.68(1H, dd, J=8.1, 0.8Hz), 4.20(1H,br), 2.97(2H, q, J=7.7Hz), 2.54-2.39(2H, m), 2.15-2.01(2H, m), 1.43(3H,t, J=7.7Hz), 0.84(6H, t, J=7.5Hz). MS(NH₃—CI): m/e 400(7), 399(37),398(26), 397(100). Example 524 spectral data: TLC R_(F) 0.50(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃: δ8.89(1H, s), 7.76(1H, d,J=9.1Hz), 6.90-6.87(2H, m), 4.35(1H, v br), 3.86(3H, s), 2.93(2H, q,J=7.6Hz), 2.48(3H, s), 2.39(2H, br), 2.00-1.90(2H, m), 1.43(3H, t,J=7.6Hz), 1.38-1.22(2H, m), 1.18-1.02(2H, m), 0.90(6H, t, J=7.3Hz).MS(NH₃—CI): m/e calc'd for C₂₂H₃₁N₄O: 367.2498, found 367.2506; 369(3),# 368(25), 367(100). Example 526 spectral data: TLC R_(F) 0.28(10:90ethyl acetate-hexane). ¹H HMR(300MHz, CDCl₃): δ8.91(1H, s), 7.69(1H, d,J=8.1Hz), 7.34-7.30(2H, m), 4.40-4.35(1H, m), 2.93(2H, q, J=7.4Hz),2.44(3H, s), 2.38(2H, m), 1.96(2H, m), 1.43(3H, t, J=7.5Hz),1.35-1.22(2H, m), 1.15-1.05(2H, m), 0.90(6H, t, J=7.1Hz). MS(NH₃—CI):m/e 374(8), 373(35), 372(25), 371(100). Analysls calc'd fcr C₂₁H₂₇N₄Cl:# C, 68.00; H, 7.35; N, 15.10; found: C, 67.89; H, 7.38; N, 14.94.Example 528 spectral data: TLC R_(F) 0.65(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.97(1H, s), 7.86(1H, d, J=8.0Hz), 7.82(1H, d,J=1.1Hz), 7.67(1H, dd, J=8.0, 1.1Hz), 4.38(1H, br), 2.95(2H, g,J=7.5Hz), 2.39(2H, br), 2.04-1.92(2H, br), 1.42(3H, t, J=7.5Hz),1.40-1.21(3H, m), 1.19-1.03(1H, m), 0.91(6H, t, J=7.3Hz). MS(NH₃—CI):m/e 428(8), 427(37), 426(27), 425(100). Example 538 spectral data: TLCR_(F) 0.56(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H,s), 7.88(1H, d, J=8.0Hz), 7.83(1H, d, J=0.8Hz), 7.68(1H, dd, J=8.0,0.8Hz), 3.77(1H, br), 2.95(2H, q, J=7.5Hz), 2.61(1H, br), 2.08(1H, br),1.45(3H, t, J=7.5Hz), 1.36-1.25(1H, m), 1.17(3H, d, J=6.6Hz), 0.71(3H,t, J=7.3Hz), 0.69(3H, d, J=7.0Hz). MS(NH₃—CI): m/e 414(7), 413(33),412(24), 411(100). Example 534 spectral data: MS(ESI): m/e 363(M+2),361(M⁺, 100%). Example 544 spectral data: TLC R_(F) 0.63(50:50 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 7.74(1H, d,J=9.1Hz), 6.89-6.86(2H, m), 3.86(3H, s), 3.79-3.73(1H, m), 2.93(3H, dq,J=7.7, 2.6Hz), 2.49(3H, s), 2.03-1.99(1H, m), 1.81(3H, d, J=6.9Hz),1.41(3H, t, J=7.3Hz), 0.84-0.74(2H, m), 0.53-0.41(2H, m), 0.28-0.21(1H,m). Example 548 spectral data: TLC R_(F) 0.42(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.99(1H, s), 7.84(1H, d,J=7.7Hz), 7.82(1H, d, J=0.9Hz), 7.68(1H, dd, J=7.7, 0.9Hz),3.83-3.70(1H, m), 3.00-2.90(2H, m), 2.09-1.98(1H, m), 1.83(3H, d,J=7.0Hz), 1.40(3H, t, J=7.3Hz), 0.88-0.78(1H, m), 0.57-0.41(2H, m),0.30-0.20(1H, m), MS(NH₃—CI): m/e 398(6), 397(31), 396(22), 395(100).Example 551 spectral data: TLC R_(F) 0.56(50:50 ethyl acetate-hexane).¹H NMR(300MHz, CCDl₃): δ8.93(1H, s), 6.94(2H, s), 4.75(1H, heptet,J=7.0Hz), 2.95(2H, q, J=7.7Hz), 2.32(3H, s), 2.04(6H, s), 1.80(6H, d,J=7.0Hz), 1.36(3H, t, J=7.7Hz). MS(NH₃—CI): m/e 311(4), 310(34),309(100); Analysis calc'd for C₁₉H₂₄N₄.0.5H₂O: C, 71.89; H, 7.94; N,17.65; found: C, 71.59; H, 7.83; N, 17.41. Example 558 spectral data:TLC R_(F) 0.53(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CCDl₃):δ8.98(1H, s), 7.86-7.81(2H, m), 7.67(1H, dd, J=8.4, 1.1Hz),4.60-4.48(1H, m), 3.01-2.93(2H, m), 2.49-2.35(1H, m), 2.13-2.00(1H, m),1.76(3H, d, J=7.0Hz), 1.41(3H, t, J=7.5Hz), 1.40-1.20(4H, m), 0.87(3H,t, J=7.3Hz). MS(NH₃—CI): m/e 414(8), 413(38), 412(27), 411(100). Example564 spectral data: TLC R_(F) 0.34(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CCDl₃): δ8.89(1H, s), 7.77(1H, d, J=9.2Hz), 6.89(2H, m),4.30-4.20(1H, m), 3.86(3H, s), 2.93(2H, q, J=7.5Hz), 2.48(3H, s),2.45-2.35(2H, m), 2.10-1.95(2H, m), 1.44(3H, t, J=7.5Hz), 1.40-1.20(3H,m), 1.10—0.95(1H, m), 0.84(3H, t, J=7.3Hz), 0.81(3H, t, J =7.3Hz).Example 571 spectral data: TLC R_(F) 0.40(50:50 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.89(1H, s), 6.95(2H, s), 4.51(1H, br),3.44-3.24(4H, m), 2.96(2H, q, J=7.3Hz), 2.95-2.87(1H, m), 2.85-2.75(1H,m), 2.59-2.49(1H, m), 2.32(3H, s), 2.27-2.18(1H, m), 2.04(3H, s),2.04(3H, s), 1.38(3H, t, J=7.7Hz), 1.12(3H, t, J=7.0Hz), 0.84(3H, t,J=7.3Hz), MS(NH₃—CI): m/e calc'd for C₂₃H₃₂N₄O: # 380.2576, found380.2554; 383(4), 362(26), 381(100). Example 581 spectral data: TLCR_(F) 0.33(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.89(1H,s), 6.95(2H, s), 4.49-4.39(1H, m), 4.23-4.13(1H, m), 3.91(1H, dd, J=9.9,4.8Hz), 3.48(1H, dq, J=9.1, 7.0Hz), 3.30(1H, dq, J=9.1, 7.0Hz), 2.95(2H,q, J=7.7Hz), 2.60-2.47(1H, m), 2.32(3H, s), 2.15-2.01(1H, m), 2.04(3H,s), 2.03(3H, s), 1.37(3H, t, J=7.5Hz), 1.00(3H, t, J=7.0Hz), # 0.86(3H,t, J=7.3Hz). MS(NH₃—CI): m/e calc'd for C₂₂H₃₁N₄O: 367.2498, found367.2497; 369(4), 368(27), 367(100). Example 591 spectral data: TLCR_(F) 0.42(50:50 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H,s), 6.95(2H, s), 3.76(1H, br), 3.47-3.40(1H, m), 3.21(3H, s),2.99-2.90(1H, m), 2.88(2H, q, J=7.3Hz), 2.76(1H, br), 2.51-2.41(1H, m),2.32(3H, s), 2.09(1H, br), 2.08(3H, s), 2.04(3H, s), 1.35(3H, t,J=7.3Hz), 0.84-0.76(1H, m), 0.56-0.44(2H, m), 0.30-0.21(1H, m).MS(NH₃—CI): m/e calc'd for # C₂₃H₃₁N₄O: 379.2498, found 379.2514;381(4), 380(27), 379(100). Example 690 spectral data: TLC R_(F)0.12(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ9.01(1H, s),7.38-7.22(5H, m), 6.75(1H, s), 6.69(1H, s), 5.48(2H, s), 3.70(3H, s),2.84(2H, q, J=7.7Hz), 2.37(3H, s), 2.05(3H, s), 1.26(3H, t, J=7.7Hz).MS(NH₃—CI): m/e 375(4), 374(28), 373(100). Example 692 spectral data:TLC R_(F) 0.32(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.98(1H, s), 7.48(1H, s), 7.37-7.18(5H, m), 7.11(1H, s), 5.49(2H, s),2.84(2H, q, J=7.3Hz), 2.38(3H, s), 2.29(6H, s), 1.31(3H, t, J=7.3Hz).MS(NH₃—CI): m/e calc'd for C₂₃H₂₄N₄: 356.2001, found 356.1978; 359(4),358(28), 357(100). Example 693 spectral data: TLC R_(F) 0.22(20:80 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 7.78(1H, d,J=9.5Hz), 6.90-6.87(2H, m), 3.86(3H, s), 3.62(1H, br), 2.91(2H, q,J=7.5Hz), 2.50(3H, s), 2.40(1H, br), 2.26-2.13(1H, m), 1.92(1H, br),1.58(1H, br), 1.43(3H, t, J=7.5Hz), 1.35-1.25(1H, m), 1.13-1.03(1H, m),0.95-0.75(2H, m), 0.85(3H, t, J=7.1Hz), 0.54-0.42(2H, m), 0.22-0.17(1H,# m). MS(NH₃—CI): m/e 381(4), 380(25), 379(100). Example 697 spectraldata: TLC R_(F) 0.28(30:70 ethyl acetate-hexane). ¹H NNR(300MHz, CDCl₃):δ8.89(1H, s), 7.74(1H, d, J=9.5Hz), 6.90-6.86(2H, m), 4.58-4.45(1H, m),2.95(2H, dq, J=7.7, 2.2Hz), 2.48(3H, s), 2.45-2.35(1H, m), 2.09-1.99(1H,m), 1.74(3H, d, J=7.0Hz), 1.42(3H, t, J=7.5Hz), 1.37-1.23(3H, m),1.11-1.03(1H, m), 0.86(3H, t, J=7.0Hz). Example 724 spectral data: TLCR_(F) 0.45(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.92(1H,s), 7.75(1H, d, J=8.4Hz), 7.09(1H, d, J=2.6Hz), 6.96(1H, dd, J=8.4,2.6Hz), 3.87(3H, s), 3.76(1H, br), 2.94(2H, q, J=7.3Hz), 2.61(1H, br),2.09(1H, br), 1.45(3H, t, J=7.3Hz), 1.36-1.26(1H, m), 1.15(3H, d,J=6.6Hz), 0.71(3H, t, J=7.3Hz), 0.68(3H, d, J=6.6Hz). MS(NH₃—CI): m/e377(1), # 376(8), 375(38), 374(25), 373(100). Example 725 spectral data:TLC R_(F) 0.31(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.88(1H, s), 7.80(1H, d, J=9.2Hz), 6.89(2H, m), 3.86(3H, s), 3.75(1H,m), 2.92(2H, q, J=7.4Hz), 2.60(1H, m), 2.48(3H, s), 2.05(1H, m),1.46(3H, t, J=7.4Hz), 1.16(3H, d, =7.0Hz), 0.70(3H, t, J=7.3Hz),0.67(3H, d, J=6.6Hz). Example 727 spectral data: TLC R_(F) 0.44(30:70ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 7.84(1H, d,=2.2Hz), 7.74(1H, d, J=8.4Hz), 7.65(1H, dd, J=8.4, 2.2Hz), 3.76(1H, br),2.93(1H, q, J=7.3Hz), 2.60(1H, br), 2.08(1H, br), 1.42(3H, t, J=7.3Hz),1.37-1.27(1H, m), 1.16(3H, d, J=7.0Hz), 0.69(3H, t, J=7.3Hz), 0.67(3H,d, J=7.0Hz). MS(NH₃—CI): m/e 414(7), 413(33), 412(27), 411(100). Example750 spectral data: TLC R_(F) 0.42(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.94(1H, s), 7.73(1H, d, J=8.4Hz), 7.10(1H, d,J=2.6Hz), 6.96(1H, dd, J=8.4, 2.6Hz), 3.87(3H, s), 3.63(1H, v br),2.92(2H, q, J=7.3Hz), 2.38(1H, br), 2.22-2.10(1H, m), 1.94(1H, br),1.42(3H, t, J=7.3Hz), 1.41-1.29(1H, m), 1.23-1.08(1H, m), 0.91(3H, t,J=7.3Hz), 0.89-0.79(1H, m), 0.51-0.41(2H, m), # 0.25-0.15(1H, m).MS(NH₃—CI): m/e 388(8), 387(34), 386(25), 385(100). Example 751 spectraldata: TLC R_(F) 0.36(40:60 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.89(1H, s), 7.77(1H, d, J=9.1Hz), 6.90(2H, m), 3.86(3H, s), 3.62(1H,m), 2.84(2H, q, J=7.5Hz), 2.49(3H, s), 2.40(1H, m), 2.19(1H, m),1.90(1H, m), 1.43(3H, t, J=7.5Hz), 1.38(1H, m), 1.19(1H, m), 0.91(3H, t,J=7.3Hz), 0.80(1H, m), 0.49(2H, m), 0.21(1H, m). Example 753 spectraldata: TLC R_(F) 0.44(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.92(1H, s), 7.84(1H, d, J=1.8Hz), 7.73(1H, d, J=8.5Hz), 7.65(1H, dd,J=8.5, 1.8Hz), 3.65(1H, br), 2.92(1H, q, J=7.5Hz), 2.38(1H, br),2.25-2.14(1H, m), 1.94(1H, br), 1.43-1.26(1H, m), 1.40(3H, t, J=7.5Hz),1.21-1.06(1H, m), 0.92(3H, t, J=7.3Hz), 0.91-0.79(1H, m), 0.52-0.44(2H,m), 0.22-0.16(1H, m). # MS(NH₃—CI): m/e 426(9), 425(42), 424(31),423(100). Example 767 spectral data: MS(NH₃—CI): m/e 379(M+H⁺, 100%).Example 776 spectral data: TLC R_(F) 0.41(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 7.73(1H, d, J=8.4Hz) 7.09(1H, d,J=2.6Hz), 6.96(1H, dd, J=8.4, 2.6Hz), 4.28(1H, br), 3.87(3H, s),2.95(2H, q, J=7.3Hz), 2.41(2H, br), 2.10-1.93(2H, m), 1.43(3H, t,J=7.3Hz), 1.40-1.23(1H, m), 1.18-1.03(1H, m), 0.91(3H, t, J=7.3Hz),0.82(3H, t, J=7.5Hz). MS(NH₃—CI): m/e calc'd for # C₂₀H₂₈ClN₄O:373.1795, found 373.1815; 376(8), 375(35), 374(24), 373(100). Example777 spectral data: TLC R_(F) 0.46(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.89(1H, s), 7.76(1H, d, J=9.0Hz), 6.90-6.87(2H,m), 4.29(1H, br), 3.86(3H, s), 2.94(2H, q, J=7.4Hz), 2.48(3H, s),2.40(2H, br), 2.10-1.92(2H, m), 1.44(3H, t, J=7.4Hz), 1.37-1.22(1H, m),1.18-1.02(1H, m), 0.90(3H, t, J=7.3Hz), 0.81(3H, t, J=7.3Hz).MS(NH₃—CI): m/e calc'd for C₂₁H₂₉N₄O: # 353.2341, found 353.2328;355(3), 354(23), 353(100). Example 778 spectral data: TLC R_(F)0.58(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.97(1H, s),7.86(1H, d, J=8.0Hz), 7.83(1H, d, J=0.8Hz), 7.68(1H, dd, J=8.0, 0.8Hz),4.30(1H, br), 2.96(2H, q, J=7.5Hz), 2.41(2H, br), 2.11-1.95(2H, m),1.43(3H, t, J=7.5Hz), 1.42-1.22(2H, m), 0.92(3H, t, J=7.3Hz), 0.83(3H,t, J=7.3Hz). MS(NH₃—CI): m/e 414(8), 413(39), 412(28), 411(100). Example779 spectral data: TLC R_(F) 0.44(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.91(1H, s), 7.84(1H, d, J=1.8Hz), 7.72(1H, d,J=8.0Hz), 7.65(1H, dd, J=8.0, 1.8Hz), 4.31(1H, br), 2.94(1H, q,J=7.5Hz), 2.40(2H, br), 2.10-1.93(2H, m), 1.40(3H, t, J=7.5Hz),1.37-1.21(1H, m), 1.19-1.02(1H, m), 0.91(3H, t, J=7.3Hz), 0.81(3H, t,J=7.3Hz). MS(NH₃—CI): m/e 414(9), 413(43), 412(31), 411(100). Example793 spectral data: MS(NH₃—CI): m/e 367(M+H⁺, 100%). Example 799 spectraldata: TLC R_(F) 0.61(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.90(1H, s), 7.47(1H, s), 7.10(1H, s), 4.28(1H, br), 2.93(2H, q,J=7.3Hz), 2.41(1H, br), 2.36(3H, s), 2.28(6H, s), 2.07-1.91(3H, m),1.42(3H, t, J=7.3Hz), 1.35-1.21(1H, m), 1.19-1.03(1H, m), 0.90(3H, t,J=7.2Hz), 0.81(3H, t, J=7.3Hz). MS(NH₃—CI): m/e calc'd for C₂₂H₃₀N₄:350.2470, found 350.2476; # 353(3), 352(24), 351(100). Example 802spectral data: TLC R_(F) 0.38(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ8.92(1H, s), 7.84(1H, d, J=1.8Hz), 7.73(1H, d,J=8.4Hz), 7.65(1H, dd, J=8.4, 1.8Hz), 3.53(1H, br), 2.91(1H, q,J=7.4Hz), 2.52-2.35(1H, m), 2.34-2.20(1H, m), 1.95(1H, br), 1.40(3H, t,J=7.4Hz), 0.89-0.79(1H, m), 0.87(3H, t, J=7.3Hz), 0.55-0.42(2H, m),0.25-0.15(1H, m). MS(NH₃—CI): m/e 412(8), 411(41), 410(29), 409(100).Example 803 spectral data: TLC R_(F) 0.33(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 7.85(1H, d, J=2.2Hz), 7.71(1H, d,J=8.4Hz), 7.64(1H, dd, J=6.4, 2.2Hz), 3.77(1H, dq, J=9.9, 7.0Hz),2.93(1H, dq, J=7.5, 2.0Hz), 2.09-1.98(1H, m), 1.82(3H, d, J=7.0Hz),1.39(3H, t, J=7.5Hz), 0.86-0.78(1H, m), 0.59-0.50(1H, m), 0.49-0.40(1H,m), 0.29-0.20(1H, m). MS(NH₃—CI): m/e 399(2), 398(8), 397(39), 396(24),395(100). Example 804 spectral data: TLC R_(F) 0.31(20:80 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.92(1H, s), 7.84(1H, d,J=1.8Hz), 7.71-7.62(2H, m), 4.55(1H, m), 2.95(2H, q, J=7.5Hz),2.43-2.32(1H, m), 2.10-1.98(1H, m), 1.75(3H, d, J=7.0Hz), 1.39(3H, t,J=7.5Hz), 1.38-1.27(1H, m), 1.19-1.09(1H, m), 0.93(3H, t, J=7.1Hz).MS(NH₃—CI): m/e 400(7), 399(32), 398(22), 397(100). Analysis calc'd for# C₁₉H₂₀ClF₃N₄: C, 57.51; H, 5.08; N, 14.12; found: C, 57.55; H, 5.06;N, 13.95. Example 805 spectral data: TLC R_(F) 0.41(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.92(1H, s), 7.84(1H, d,J=1.8Hz), 7.70(1H, d, J=8.0Hz), 7.64(1H, dd, J=8.0, 1.8Hz),4.58-4.49(1H, m), 2.95(1H, q, J=7.5Hz), 2.45-2.33(1H, m), 2.11-2.00(1H,m), 1.75(3H, d, J=6.6Hz), 1.39(3H, t, J=7.5Hz), 1.38-1.21(4H, n),0.86(3H, t, J=7.0Hz). MS(NH₃—CI): m/e 414(8), 413(40), 412(29),411(100). Example 807 spectral data: TLC R_(F) 0.49(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H, s), 7.84(1H, d,J=1.8Hz), 7.73(1H, d, J=8.4Hz), 7.65(1H, dd, J=8.4, 1.8Hz),4.38-4.19(1H, m), 2.94(1H, q, J=7.5Hz), 2.40(2H, br), 2.10-1.98(2H, m),1.41(3H, t, J=7.5Hz), 1.38-1.20(3H, m), 1.09-0.99(1H, m), 0.84(3H, t,J=7.0Hz), 0.81(3H, t, J=7.5Hz). MS(NH₃—CI): m/e 428(7), 427(32),426(25), 425(100). Example 808 spectral data: TLC R_(F) 0.51(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H, s), 7.84(1H, d,J=1.8Hz), 7.72(1H, d, J=8.4Hz), 7.64(1H, dd, J=8.4, 1.8Hz), 4.37(1H,br), 2.93(1H, q, J=7.5Hz), 2.38(2H, br), 2.02-1.90(2H, m), 1.40(3H, t,J=7.5Hz), 1.38-1.20(2H, m), 1.18-1.01(2H, m), 0.90(6H, t, J=7.3Hz).MS(NH₃—CI): m/e 428(8), 427(39), 426(30), 425(100). Example 809 spectraldata: TLC R_(F) 0.40(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.90(1H, s), 7.84(1H, d, J=2.2Hz), 7.72(1H, d, J=8.1Hz), 7.65(1H, dd,J=8.1, 2.2Hz), 4.20(1H, br), 2.94(1H, q, J=7.5Hz), 2.51-2.38(2H, m),2.13-2.00(2H, m), 1.41(3H, t, J=7.5Hz), 0.82(6H, t, J=7.5Hz).MS(NH₃—CI): m/e 400(7), 399(36), 398(25), 397(100). Example 824 spectraldata: TLC R_(F) 0.27(20:80 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.94(1H, s), 8.10(1H, s), 7.94(1H, d, J=8.8Hz), 7.87(1H, d, J=8.1Hz),4.56(1H, m), 2.96(2H, q, J=7.5Hz), 2.40(1H, m), 2.10-2.00(1H, m),1.76(3H, d, J=7.0Hz), 1.39(3H, t, J=7.5Hz), 1.33-1.10(2H, m), 0.93(3H,t, J=7.1Hz). ¹⁹F NMR(300MHz, CDCl₃): δ−58.2, −63.4. MS(NH₃—CI): m/e433(3), 432(24), 431(100). Example 832 spectral data: TLC R_(F)0.34(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.94(1H, s),7.73(1H, d, J=8.5Hz), 7.10(1H, d, J=2.6Hz), 6.96(1H, dd, J=8.5, 2.6Hz),3.87(3H, s), 3.55(1H, br), 2.92(2H, q, J=7.3Hz), 2.53-2.35(1H, m),2.31-2.18(1H, m), 1.96(1H, br), 1.42(3H, t, J=7.3Hz), 0.87(3H, t,J=7.5Hz), 0.87-0.79(1H, m), 0.53-0.43(2H, m), 0.25-0.15(1H, m).MS(NH₃—CI): m/e 374(8), 373(34), 372(24), 371(100). Example 833 spectraldata: TLC R_(F) 0.20(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.96(1H, s), 7.70(1H, d, J=8.4Hz), 7.10(1H, d, J=2.5Hz), 6.96(1H, dd,J=8.4, 2.5Hz), 4.16(2H, d, J=7.0Hz), 3.87(3H, s), 3.01(2H, q, J=7.3Hz),1.46(3H, t, J=7.3Hz), 1.37-1.27(1H, m), 0.66-0.52(4H, m). MS(NH₃—CI):m/e 346(6), 345(32), 344(23), 343(100). Example 834 spectral data: TLCR_(F) 0.18(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.94(1H,s), 7.69(1H, d, J=8.4Hz), 7.09(1H, d, J=1Hz), 6.96(1H, dd, J=8.4, 1Hz),4.60-4.50(1H, m), 3.87(3H, s), 2.97(2H, q, J=7.3Hz), 2.49-2.33(1H, m),2.09-1.97(1H, m), 1.74(3H, d, J=7.0Hz), 1.41(3H, t, J=7.5Hz),1.40-1.22(1H, m), 1.21-1.09(1H, m), 0.92(3H, t, J=7.1Hz). MS(NH₃—CI):m/e calc'd for # C₁₉H₂₄ClN₄O: 359.1639, found 359.1623; 362(7), 361(33),360(23), 359(100). Analysis calc'd for C₁₉H₂₃ClN₄O.0.5H₂O: C, 62.20; H,6.32; N, 15.27; found: C, 62.33; H, 6.36; N, 14.86. Example 835 spectraldata: TLC R_(F) 0.39(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.94(1H, s), 7.69(1H, d, J=8.4Hz), 7.09(1H, d, J=2.5Hz), 6.95(1H, dd,J=8.4, 2.5Hz), 4.53-4.47(1H, m), 3.87(3H, s), 3.01-2.92(2H, m),2.48-2.35(1H, m), 2.11-1.99(1H, m), 1.74(3H, d, J=6.9Hz), 1.41(3H, t,J=7.5Hz), 1.38-1.22(3H, m), 1.14-1.00(1H, m), 0.86(3H, t, J=7.1Hz).MS(NH₃—CI): m/e 376(7), 375(33), 374(23), 373(100). Example 836 spectraldata: TLC R_(F) 0.42(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.94(1H, s), 7.79(1H, d, J=8.8Hz), 7.09(1H, d, J=2.5Hz), 6.95(1H, dd,J=8.8, 2.5Hz), 4.55-4.47(1H, m), 3.87(3H, s), 3.01-2.92(2H, m),2.48-2.35(1H, m), 2.10-1.97(1H, m), 1.74(3H, d, J=7.0Hz), 1.41(3H, t,J=7.5Hz), 1.35-1.20(5H, m), 1.18-1.02(1H, m), 0.84(3H, t, J=7.0Hz).MS(NH₃—CI): m/e calc'd for C₂₁H₂₈ClN₄O: 387.1952, found 387.1944;391(1), 390(8), 389(35), 388(25), 387(100). Example 837 spectral data:TLC R_(F) 0.45(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.93(1H, s), 7.73(1H, d, J=8.8Hz), 7.09(1H, d, J=2.6Hz), 6.96(1H, dd,J=8.8, 2.6Hz), 4.25(1H, br), 3.87(3H, s), 2.95(2H, q, J=7.3Hz), 2.41(2H,br), 2.10-2.00(2H, m), 1.43(3H, t, J=7.3Hz), 1.37-1.20(3H, m),1.12-0.98(1H, m), 0.84(3H, t, J=7.3Hz), 0.82(3H, t, J=7.4Hz).MS(NH₃—CI): m/e 390(8), 389(34), 388(25), 387(100). Example 838 spectraldata: TLC R_(F) 0.48(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.94(1H, s), 7.72(1H, d, J=8.5Hz), 7.09(1H, d, J=2.2Hz), 6.96(1H, dd,J=8.5, 2.2Hz), 4.36(1H, v br), 3.87(3H, s), 2.94(2H, q, J=7.3Hz),2.39(2H, br), 2.02-1.90(2H, m), 1.42(3H, t, J=7.3Hz), 1.39-1.21(2H, m),1.18-1.03(2H, m), 0.90(6H, t, J=7.3Hz). MS(NH₃—CI): m/e calc'd forC₂₁H₂₈ClN₄O: 387.1952, found 387.1958; 391(1), # 390(8), 389(34),388(26), 387(100). Example 839 spectral data: TLR R_(F) 0.36(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 7.73(1H, d,J=8.5Hz), 7.09(1H, d, J=2.6Hz), 6.96(1H, dd, J=8.5, 2.6Hz), 4.19(1H, brs), 3.87(3H, s), 2.96(2H, q, J=7.5Hz), 2.52-2.38(2H, m), 2.03-1.99(2H,m), 1.43(3H, t, J=7.5Hz), 0.83(6H, t, J=7.3Hz). MS(NH₃—Cl): m/e calc'dfor C₁₉H₂₄ClN₄O: 359.1639, found 359.1632; 362(7), 361(34), 360(23),359(100). Example 870 spectral data: MS(NH₃—CI): m/e 423(M+H⁺, 100%).Example 900 spectral data: TLC R_(F) 0.38(50:50 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 7.75(1H, d, J=9.2Hz), 6.90-6.86(2H,m), 4.23(2H, t, J=7.7Hz), 3.86(3H, s), 2.95(2H, q, J=7.7Hz), 2.48(3H,s), 1.93-1.83(2H, m), 1.45(3H, t, J=7.6Hz), 1.43-1.36(4H, m), 0.92(3H,t, J=7.0Hz). Example 902 spectral data: TLC R_(F) 0.28(5:95 ethylacetate-dichloromethane). ¹H NMR(300MHz, CDCl₃): δ8.94(1H, s), 7.63(1H,d, J=8.1Hz), 7.37(1H, d, J=1.0Hz), 7.21(1H, dd, J=8.1, 1.0Hz), 4.38(1H,br), 2.94(2H, q, J=7.5Hz), 2.41(3H, s), 2.40(2H, br), 2.00-1.90(2H, m),1.42(3H, t, J=7.5Hz), 1.35-1.22(2H, m), 1.17-1.03(2H, m), 0.90(6H, t,J=7.3Hz). MS(NH₃—CI): m/e calc'd for C₂₁H₂₈ClN₄: 371.2002, # found371.1993; 374(8), 373(34), 372(25), 371(100). Example 944 spectral data:MS(NH₃—CI): m/e 377(M+H⁺, 100%). Example 945 spectral data: MS(NH₃—CI):m/e 365(M+H⁺, 100%). Example 947 spectral data: MS(NH₃—CI): m/e353(M+H⁺, 100%). Example 951 spectral data: MS(NH₃—CI): m/e 381(M+H⁺,100%). Example 952 spectral data: MS(NH₃—CI): m/e 353(M+H⁺, 100%).Example 1003 spectral data: TLC R_(F) 0.10(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.99(1H, s), 7.43(1H, s), 7.19(2H, d, J=8.8Hz),6.86(2H, d, J=8.8Hz), 6.84(1H, s), 5.42(2H, s), 3.94(3H, s), 3.91(3H,s), 3.78(3H, s), 2.86(2H, q, J=7.7Hz), 2.45(3H, s), 1.35(3H, t,J=7.7Hz). MS(NH₃—CI): m/e 421(4), 420(27), 419(100). Analysis calculatedfor C₂₄H₂₆N₄O₃: C, 68.88; H, 6.26; N, 13.39; found: C, 68.53; H, 6.30;N, 12.96. Example 1012 spectral data: m.p. 147-148° C. TLC R_(F)0.18(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.88(1H, s),7.60(1H, s), 6.77(1H, s), 4.61(2H, t, J=8.6Hz), 3.44(1H, v br), 3.24(2H,t, J=8.6Hz), 2.94(2H, br), 2.44(3H, s), 2.03(2H, v br), 1.45(3H, br t,J=6Hz), 0.89-0.79(2H, m), 0.58(2H, br), 0.50-0.40(2H, m), 0.27-0.17(2H,m). MS(NH₃—CI): m/e 377(4), 376(27), 375(100). Analysis calc'd # forC₂₃H₂₆N₄O: C, 73.77; H, 7.01; N, 14.96; found: C, 73.69; H, 7.08; N,14.40. Example 1023 spectral data: TLC R_(F) 0.22(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ9.04(1H, s), 7.78(1H, d,=8.4Hz), 7.44(1H, d, J=1.1Hz), 7.30(1H, J=8.4, 1.1Hz), 7.20(2H, d,J=8.5Hz), 6.87(2H, d, =8.5Hz), 5.44(2H, s), 3.79(3H, s), 2.90(2H, q,J=7.5Hz), 1.32(3H, t, J=7.5Hz). MS(NH₃—CI): m/e 467(1), 466(8), 465(35),464(27), 463(100). Example 1027 spectral data: TLC R_(F) 0.41(25:75ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H, s), 7.76(1H, d,J=8.4Hz), 7.45-7.44(1H, m), 7.27(1H, dm, J=8Hz), 4.61-4.51(1H, m),2.98(2H, dq, J=7.5, 1.6Hz), 2.48-2.35(1H, m), 2.10-1.98(1H, m), 1.75(3H,d, J=7.0Hz), 1.41(3H, t, J=7.5Hz), 1.35-1.22(2H, m), 0.93(3H, t,J=7.2Hz). MS(NH₃—CI): m/e calculated for C₁₉H₂₁ClF₃N₄O: 413.1349, found# 413.1344; 416(8), 415(35), 414(24), 413(100). Example 1028 spectraldata: TLC R_(F) 0.45(25:75 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃):δ8.96(1H, s), 7.77(1H, d, J=8.4Hz), 7.44(1H, m), 7.27(1H, dm, J=8Hz),4.57-4.49(1H, m), 2.97(2H, dq, J=7.7, 1.7Hz), 2.47-2.36(1H, m),2.12-2.02(1H, m), 1.75(3H, d, J=7.0Hz), 1.41(3H, t, J=7.7Hz),1.33-1.21(4H, m), 0.86(3H, t, J=7.3Hz). MS(NH₃—CI): m/e calculated forC₂₀H₂₃ClF₃N₄O: 427.1509, found 427.1507; # 430(8), 429(35), 428(25),427(100). Example 1032 spectral data: TLC R_(F) 0.44(25:75 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.95(1H, s), 7.80(1H, d,J=8.4Hz), 7.45-7.44(1H, m), 7.30(1H, dm, J=8Hz), 4.23-4.17(1H, m),2.97(2H, q, J=7.6Hz), 2.54-2.39(2H, m), 2.14-2.00(2H, m), 1.43(3H, t,J=7.6Hz), 0.84(6H, t, J=7.3Hz). MS(NH₃—CI): m/e calculated forC₁₉H₂₁ClF₃N₄O: 413.1368, found 413.1373; 416(8), 415(34), 414(24),413(100). Example 1150 spectral data: TLC R_(F) 0.23(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.90(1H, s), 7.73(1H, d,J=8.8Hz), 7.36(1H, d, J=2.6Hz), 7.17(1H, dd, J=8.8, 2.6Hz), 3.92(3H, s),3.70-3.55(1H, m), 2.91(2H, q, J=7.4Hz), 2.45-2.35(1H, m), 2.25-2.15(1H,m), 2.00-1.90(1H, m), 1.40(3H, t, J=7.4Hz), 1.40-1.30(1H, m),1.20-1.10(1H, m), 0.91(3H, t, J=7.2Hz), 0.87-0.77(1H, m), 0.54-0.44(2H,m), 0.25-0.15(1H, m). # MS(NH₃—CI): m/e calc'd for C₂₂H₂₆F₃N₄O:419.2057; found 419.2058; 421(3), 420(26), 419(100). Example 1153spectral data: TLC R_(F) 0.48(30:70 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ9.00(1H, s), 7.89(1H, d, J=8.0Hz), 7.84(1H, s),7.69(1H, d, J=8.0Hz), 7.40-7.30(5H, m), 5.14(1H, d, J=10.2Hz), 2.82(1H,dq, J=15.5, 7.7Hz), 2.68(1H, dq, J=15.5, 7.7Hz), 2.15(1H, br), 1.23(3H,t, J=7.7Hz), 1.13-1.03(1H, m), 0.78-0.62(2H, m), 0.53-0.43(1H, m).MS(NH₃—CI): m/e calculated for # C₂₄H₂₁ClF₃N₄: 457.1407, found 457.1389;460(9), 459(35), 458(29), 457(100). Example 1155 spectral data: TLCR_(F) 0.46(25:75 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.98(1H,s), 7.83(1H, d, J=8.4Hz), 7.46-7.27(7H, m), 5.13(1H, d, J=10.7Hz),2.88-2.62(2H, m), 2.15(1H, br), 1.26(3H, t, J=7.5Hz), 1.12-1.02(1H, m),0.78-0.62(2H, m), 0.54-0.44(1H, m). MS(NH₃—CI): m/e calculated forC₂₄H₂₁ClF₃N₄O: 473.1361, found 473.1365; 476(9), 475(36), 474(29),473(100). Example 1157 spectral data: TLC R_(F) 0.19(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.93(1H, s), 7.77(1H, d,J=8.8Hz), 7.40-7.30(6H, m), 7.19(1H, dd, J=8.8, 2.2Hz), 5.13(1H, d,J=10.6Hz), 3.92(3H, s), 2.79(1H, dq, J=15, 7.7Hz), 2.64(1H, dq, J=15,7.7Hz), 2.12(1H, br), 1.21(3H, t, J=7.7Hz), 1.10-1.00(1H, m),0.77-0.62(2H, m), 0.55-0.45(1H, m). MS(NH₃—CI): m/e calc'd forC₂₅H₂₄F₃N₄O: # 453.1902, found 453.1903; 455(4), 454(28), 453(100).Example 1158 spectral data: TLC R_(F) 0.16(20:80 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ8.98(1H, s), 7.46-7.25(7H, m), 5.12(1H, br d,J=9Hz), 2.85-2.62(2H, m), 2.14(1H, br), 2.13(3H, d, J=0.7Hz), 1.18(3H,dq, J=7.7, 4.1Hz), 0.75-0.35(4H, m). MS(NH₃—CI): m/e calc'd forC₂₄H₂₃Cl₂N₄: 437.1300, found 437.1294; 440(19), 439(67), 438(32),437(100). Example 1161 spectral data: MS(NH₃—CI): m/e 441(M+H⁺, 100%).Example 1163 spectral data: TLC R_(F) 0.44(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ9.00(1H, s), 7.89(1H, d, 8.4Hz), 7.84(1H, s),7.69(1H, d, J=8.4Hz), 7.38(2H, d, J=9Hz), 7.05(2H, d, J=9Hz), 5.08(1H,d, J=10.2Hz), 2.82(1H, dq, J=15.5, 7.7Hz), 2.68(1H, dq, J=15.5, 7.7Hz),2.14(1H, m), 1.25(3H, t, J=7.7Hz), 1.10-1.01(H, m), 0.74-0.62(2H, m),0.51-0.41(1H, m). MS(NH₃—CI): m/e calculated for # C₂₄H₂₀ClF₄N₄:475.1313, found(30), 475(100). Example 1222 spectral data: MS(NH₃—CI):m/e 363(M+H⁺, 100%). Example 1252 spectral data: TLC R_(F) 0.24(20:80ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.72(1H, s), 7.87(1H, dd,J=8.8, 5.5Hz), 7.46(1H, dd, J=8.8, 2.5Hz), 7.35-7.26(1H, m),7.24-7.18(6H, m), 7.08-7.01(4H, m), 4.89-4.79(1H, m), 4.49(2H, d,J=12.1Hz), 4.37(2H, d, J=12.1Hz), 4.27(2H, t, J=9.3Hz), 4.01(2H, dd,J=9.9, 5.2Hz), 2.98(2H, q, J=7.7Hz), 1.39(3H, t, J=7.7Hz). MS(NH₃—CI):m/e # calc'd for C₃₁H₂₉F₆N₄O₂: 565.2227, found 565.2226; 567(7),566(36), 565(100). Example 1255 spectral data: TLC R_(F) 0.50(25:75ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.96(1H, s), 7.80(1H, d,J=8.4Hz), 7.45-7.43(1H, m), 7.31-7.27(1H, dm, J=8Hz), 3.80-3.73(1H, m),2.93(2H, q, J=7.3Hz), 2.40(1H, br), 2.25-2.14(1H, m), 1.95(1H, br),1.42(3H, t, J=7.5Hz), 1.35-1.10(2H, m), 0.92(3H, t, J=7.3Hz),0.91-0.80(1H, m), 0.53-0.44(2H, m), 0.24-0.14(1H, m). MS(NH₃—CI): m/e #calculated for C₂₁H₂₃ClF₃N₄O: 439.1519, found 439.1524; 442(8), 441(34),440(26), 439(100). Example 1256 spectral data: TLC R_(F) 0.48(25:75ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.95(1H, s), 7.79(1H, d,J=8.4Hz), 7.45-7.43(1H, m), 7.27(1H, dm, J=8Hz), 4.35-4.25(1H, m),2.96(2H, q, J=7.4Hz), 2.42(2H, br), 2.12-1.93(2H, m), 1.43(3H, t,J=7.4Hz), 1.37-1.22(2H, m), 0.91(3H, t, J=7.2Hz), 0.83(3H, t, J=7.5Hz).MS(NH₃—CI): m/e calculated for C₂₀H₂₃ClF₃N₄O: 427.1514, found 427.1515;430(8), # 429(34), 428(25), 427(100). Example 1295 spectral data: TLCR_(F) 0.37(50:50 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.91(1H,s), 7.38(1H, s), 6.83(1H, s), 4.46(1H, m, J=7.3Hz), 3.94(3H, s),3.91(3H, s), 2.96(2H, q, J=7.6Hz), 2.49-2.39(1H, m), 2.43(3H, s),2.12-2.02(1H, m), 1.75(3H, d, J=6.5Hz), 1.44(3H, t, J=7.5Hz), 0.86(3H,t, J=7.5Hz). MS(NH₃—CI): m/e calc'd for C₂₀H₂₇N₄O₂: 355.2134, found355.2139; 357(3), 356(23), 355(100). Example 1296 spectral data: TLCR_(F) 0.37(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ9.00(1H,s), 7.68(1H, d, J=8.4Hz), 7.57(1H, d, J=2.2Hz), 7.39(1H, dd, J=8.4,2.2Hz), 7.27(2H, d, J=8.4Hz), 6.89(2H, d, J=8.4Hz), 5.56(1H, dd, J=9.7,7.4Hz), 3.79(3H, s), 2.92-2.75(3H, m), 2.65-2.55(1H, m), 1.31(3H, t,J=7.5Hz), 0.92(3H, t, J=6.6Hz). MS(NH₃—CI): m/e calc'd for C₂₃H₂₃Cl₂N₄O:441.1249, found # 441.1247; 445(12), 444(18), 443(67), 442(30),441(100). Example 1319 spectral data: MS(NH₃—CI): m/e 459(M+H⁺, 100%).Example 1320 spectral data: ¹H NMR(300MHz, CDCl₃): δ8.99(s, 1H), 7.68(d,1H, J=8.4Hz), 7.58(d, 1H, J=1.9Hz), 7.42-7.3(m, 6H), 6.04(q, 1H),2.82,(m, 2H), 2.16(d, 3H, J=7.4Hz), 1.27(t, 3H, J=7.3, 7.7Hz). Example1321 7906-5 spectral data: ¹H NMR(300MHz, CDCl₃): δ9.02(s, 1H), 7.98(d,1H), 7.71(d, 1H), 7.57(d, 1H), 7.42-7.26(m, 3H), 7.15(m, 1H), 5.38(d,1H), 2.65(m, 1H), 2.4(m, 1H), 1.85(m, 1H) 1.82(s, 3H), 0.97(t, 3H),0.8(m, 2H), 0.6(m, 2H). Example 1322 spectral data: MS(NH₃—CI): m/e437(M+H⁺, 100%). Example 1323 spectral data: MS(NH₃—CI): m/e 455(M+H⁺,100%). Example 1324 spectral data: MS(ESI): m/e 425(M+H⁺), 381(M+H⁺—CO₂, 100%). Example 1325 spectral data: MS(NH₃—CI): m/e 413(M+H⁺,100%). Example 1326 spectral data: MS(NH₃—CI): m/e 427(M+H⁺, 100%).Example 1327 spectral data: MS(NH₃—CI): m/e 427(M+H⁺, 100%). Example1328 spectral data: MS(NH₃—CI): m/e 427(M+H⁺, 100%). Example 1329spectral data: MS(NH₃—CI): m/e 423(M+H⁺, 100%). Example 1330 spectraldata: MS(NH₃—CI): m/e 418(M+H⁺, 100%). Example 1331 spectral data:MS(NH₃—CI): m/e 418(M+H⁺, 100%). Example 1332 spectral data: MS(NH₃—CI):m/e 499(M+H⁺, 100%). Example 1333 spectral data: MS(NH₃—CI): m/e453(M+H⁺, 100%). Example 1334 spectral data: MS(NH₃—CI): m/e 423(M+H⁺,100%). Example 1335 spectral data: MS(NH₃—CI): m/e 372(M+H⁺, 100%).Example 1337 spectral data: MS(NH₃—CI): m/e 443(M+H⁺, 100%). Example1338 spectral data: MS(NH₃—CI): m/e 427(M+H⁺, 100%). Example 1339spectral data: MS(NH₃—CI): m/e 379(M+H⁺, 100%). Example 1341 spectraldata: MS(NH₃—CI): m/e 393(M+H⁺, 100%). Example 1342 spectral data:MS(NH₃—CI): m/e 378(M+H⁺, 100%). Example 1343 spectral data: MS(NH₃—CI):m/e 346(M+H⁺, 100%). Example 1344 spectral data: MS(NH₃—CI): m/e363(M+H⁺, 100%). Example 1346 spectral data: MS(NH₃—CI): m/e 416(M+H⁺,100%). Example 1370 spectral data: TLC R_(F) 0.23(30:70 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ8.89(1H, s), 7.72(1H, d,J=8.4Hz), 7.35(1H, d, J=2.5Hz), 7.17(1H, dd, J=8.4, 2.5Hz), 4.27(1H,br), 3.91(3H, s), 2.93(2H, q, J=7.7Hz), 2.40(2H, br), 2.10-1.95(2H, m),1.41(3H, t, J=7.7Hz), 1.39-1.27(1H, m), 1.20-1.07(1H, m), # 0.91(3H, t,J=7.3Hz), 0.81(3H, t, J=7.5Hz). MS(NH₃—CI): m/e calc'd for C₂₂H₂₆F₃N₄O:407.2058, found 407.2052; 409(3), 408(24), 407(100). Example 1371spectral data: MS(ESI): m/e 377(M+2), 375(M⁺, 100%). ^(b)Q1 =2-tetrazolyl ^(c)Q2 = 1,2,4-triazol-2-yl

TABLE 1A

(A)

(B)

(C) Ex. mp, No. R² X R³ R⁴ R¹² R¹¹ R⁶ R^(1a) R^(1b) ° C.^(a) 1043 CH₃CH₂ H CH₃ CH₃ CH₃ H CH₃ C₃H₇ oil Key: ^(a)Where the compound isindicated as an “oil”, data is provided below: Example 1043 spectraldata: TLC R_(F) 0.40 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz,CDCl₃): δ 8.91(1H, s), 7.43(1H, s), 7.10(1H, s), 4.60-4.50(1H, m),2.94(2H, dq, J=7.5, 2.0Hz), 2.45-2.35(1H, m), 2.35(3H, s), 2.28(6H, s),2.07-1.97(1H, m), 1.73(3H, d, J=6.9Hz), 1.41(3H, t, J=7.5Hz),1.40-1.27(1H, m), 1.20-1.07(1H, m), 0.92(3H, t, # J=7.3Hz). MS(NH₃—CI):m/e calc'd for C₂₃H₂₉N₄: 337.2392, found 337.2396; 339(3), 338(23),337(100). Analysis calc'd for C₂₁H₂₈N₄: C, 74.96; H, 8.40; N, 16.65;found: C, 74.28; H, 8.02; N, 16.37.

TABLE 1B

(A) (B)

(C) Ex. No. R² X R⁴ R⁵ R^(1a) R^(1b) mp, ° C.^(a) 1270 CH₃ CH₂ CF₃O(CH₂)₂— c-C₃H₅ c-C₃H₅ — OH 1271 CH₃ CH₂ CF₃ OCH₂CO₂— c-C₃H₅ c-C₃H₅ —C₂H₅ 1272 CH₃ CH₂ CF₃ OCH₂CO— c-C₃H₅ c-C₃H₅ — N(CH₃)₂ 1273 CH₃ CH₂ CF₃O(CH₂)₂— c-C₃H₅ c-C₃H₅ — NMe₃ ⁺Cl⁻ 1274 CH₃ CH₂ CF₃ OCH₂CH— c-C₃H₅c-C₃H₅ — (OH)C₂H₅ 1275 CH₃ CH₂ OCH₂OCH₃ CH₃ CH₃ C₃H₇ 77-79 1276 CH₃ CH₂OH CH₃ CH₃ C₃H₇ — 1277 CH₃ CH₂ OC₂H₅ CH₃ CH₃ C₃H₇ — 1278 CH₃ CH₂ OC₃H₇CH₃ CH₃ C₃H₇ — 1279 CH₃ CH₂ O(CH₂)₂— CH₃ CH₃ C₃H₇ — OH 1280 CH₃ CH₂OCH₂CO₂— CH₃ CH₃ C₃H₇ — C₂H₅ 1281 CH₃ CH₂ OCH₂CO— CH₃ CH₃ C₃H₇ — N(CH₃)₂1282 CH₃ CH₂ O(CH₂)₂— CH₃ CH₃ C₃H₇ — NMe₃ ⁺Cl⁻ 1283 CH₃ CH₂ OCH₂CH— CH₃CH₃ C₃H₇ — (OH)C₂H₅

TABLE 1C

Ex. mp, No. X R⁴ R⁵ R¹¹ R^(1a) R^(1b) ° C. 1501 CH₂ Cl CF₃ H C₃H₇ OCH₃76-78 1502 CH₂ Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1503 CH₂ Cl Cl H C₂H₅ C₂H₄OCH₃— 1504 CH₂ Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1505 CH₂ CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ —1506 CH₂ Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1507 CH₂ Cl COCH₃ H C₂H₅ C₂H₄OCH₃ —1508 CH₂ CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1509 CH₂ Cl CH₃ F C₂H₅ C₂H₄OCH₃ —1510 CH₂ CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1511 CH₂ CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ —1512 CH₂ Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1513 CH₂ Cl Cl H c-C₃H₅ C₂H₄OCH₃ —1514 CH₂ Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1515 CH₂ CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃— 1516 CH₂ Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1517 CH₂ Cl COCH₃ H c-C₃H₅C₂H₄OCH₃ — 1518 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1519 CH₂ Cl CH₃ Fc-C₃H₅ C₂H₄OCH₃ — 1520 CH₂ CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1521 CH₂ CH₃ CH₃CH₃ c-C₃H₅ C₂H₄OCH₃ — 1522 CH₂ Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1523 CH₂ Cl ClH C₂H₅ CH₂OCH₃ — 1524 CH₂ Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1525 CH₂ CF₃ OCH₃ HC₂H₅ CH₂OCH₃ — 1526 CH₂ Cl SO₂CH₃ H C₂H₅ CH₂OCH₃ — 1527 CH₂ Cl COCH₃ HC₂H₅ CH₂OCH₃ — 1528 CH₂ CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1529 CH₂ Cl CH₃ FC₂H₅ CH₂OCH₃ — 1530 CH₂ CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1531 CH₂ CH₃ CH₃ CH₃C₂H₅ CH₂OCH₃ — 1532 CH₂ Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1533 CH₂ Cl Cl Hc-C₃H₅ CH₂OCH₃ — 1534 CH₂ Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1535 CH₂ CF₃ OCH₃ Hc-C₃H₅ CH₂OCH₃ — 1536 CH₂ Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1537 CH₂ Cl COCH₃H c-C₃H₅ CH₂OCH₃ — 1538 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1539 CH₂ ClCH₃ F c-C₃H₅ CH₂OCH₃ — 1540 CH₂ CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1541 CH₂ CH₃CH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1542 O Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1543 O Cl ClH C₂H₅ C₂H₄OCH₃ — 1544 O Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1545 O CF₃ OCH₃ HC₂H₅ C₂H₄OCH₃ — 1546 O Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1547 O Cl COCH₃ HC₂H₅ C₂H₄OCH₃ — 1548 O CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1549 O Cl CH₃ F C₂H₅C₂H₄OCH₃ — 1550 O CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1551 O CH₃ CH₃ CH₃ C₂H₅C₂H₄OCH₃ — 1552 O Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1553 O Cl Cl H c-C₃H₅C₂H₄OCH₃ — 1554 O Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1555 O CF₃ OCH₃ H c-C₃H₅C₂H₄OCH₃ — 1556 O Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1557 O Cl COCH₃ H c-C₃H₅C₂H₄OCH₃ — 1558 O CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1559 O Cl CH₃ F c-C₃H₅C₂H₄OCH₃ — 1560 O CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1561 O CH₃ CH₃ CH₃ c-C₃H₅C₂H₄OCH₃ — 1562 O Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1563 O Cl OCH₃ H C₂H₅CH₂OCH₃ — 1564 O CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1565 O Cl SO₂CH₃ H C₂H₅CH₂OCH₃ — 1566 O Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1567 O CH₃ OCH₃ CH₃ C₂H₅CH₂OCH₃ — 1568 O Cl CH₃ F C₂H₅ CH₂OCH₃ — 1569 O CH₃ OCH₃ F C₂H₅ CH₂OCH₃— 1570 O CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1571 O Cl CF₃ H c-C₃H₅ CH₂OCH₃ —1572 O Cl Cl H c-C₃H₅ CH₂OCH₃ — 1573 O Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1574 OCF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1575 O Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1576 OCl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1577 O CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1578 OCl CH₃ F c-C₃H₅ CH₂OCH₃ — 1579 O CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1580 O CH₃CH₃ CH₃ c-C₃H₅ CH₂OCH₃ —

TABLE 1D

Ex. mp, No. X R⁴ R⁵ R¹¹ R^(1a) R^(1b) ° C. 1601 CH₂ CH₃ Cl H C₂H₅ c-C₃H₅109- 111 1602 CH₂ Cl Cl H C₂H₅ C₂H₄OCH₃ — 1603 CH₂ Cl OCH₃ H C₂H₅C₂H₄OCH₃ — 1604 CH₂ CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ — 1605 CH₂ Cl SO₂CH₃ H C₂H₅C₂H₄OCH₃ — 1606 CH₂ Cl COCH₃ H C₂H₅ C₂H₄OCH₃ — 1607 CH₂ CH₃ OCH₃ CH₃C₂H₅ C₂H₄OCH₃ — 1608 CH₂ Cl CH₃ F C₂H₅ C₂H₄OCH₃ — 1609 CH₂ CH₃ OCH₃ FC₂H₅ C₂H₄OCH₃ — 1610 CH₂ CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1611 CH₂ Cl CF₃ Hc-C₃H₅ C₂H₄OCH₃ — 1612 CH₂ Cl Cl H c-C₃H₅ C₂H₄OCH₃ — 1613 CH₂ Cl OCH₃ Hc-C₃H₅ C₂H₄OCH₃ — 1614 CH₂ CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1615 CH₂ ClSO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1616 CH₂ Cl COCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1617CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1618 CH₂ Cl CH₃ F c-C₃H₅ C₂H₄OCH₃ —1619 CH₂ CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1620 CH₂ CH₃ CH₃ CH₃ c-C₃H₅C₂H₄OCH₃ — 1621 CH₂ Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1622 CH₂ Cl Cl H C₂H₅CH₂OCH₃ — 1623 CH₂ Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1624 CH₂ CF₃ OCH₃ H C₂H₅CH₂OCH₃ — 1625 CH₂ Cl SO₂CH₃ H C₂H₅ CH₂OCH₃ — 1626 CH₂ Cl COCH₃ H C₂H₅CH₂OCH₃ — 1627 CH₂ CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1628 CH₂ Cl CH₃ F C₂H₅CH₂OCH₃ — 1629 CH₂ CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1630 CH₂ CH₃ CH₃ CH₃ C₂H₅CH₂OCH₃ — 1631 CH₂ Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1632 CH₂ Cl Cl H c-C₃H₅CH₂OCH₃ — 1633 CH₂ Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1634 CH₂ CF₃ OCH₃ H c-C₃H₅CH₂OCH₃ — 1635 CH₂ Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1636 CH₂ Cl COCH₃ Hc-C₃H₅ CH₂OCH₃ — 1637 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1638 CH₂ Cl CH₃F c-C₃H₅ CH₂OCH₃ — 1639 CH₂ CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1640 CH₂ CH₃ CH₃CH₃ c-C₃H₅ CH₂OCH₃ — 1641 O Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1642 O Cl Cl HC₂H₅ C₂H₄OCH₃ — 1643 O Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1644 O CF₃ OCH₃ H C₂H₅C₂H₄OCH₃ — 1645 O Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1646 O Cl COCH₃ H C₂H₅C₂H₄OCH₃ — 1647 O CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1648 O Cl CH₃ F C₂H₅C₂H₄OCH₃ — 1649 O CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1650 O CH₃ CH₃ CH₃ C₂H₅C₂H₄OCH₃ — 1651 O Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1652 O Cl Cl H c-C₃H₅C₂H₄OCH₃ — 1653 O Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1654 O CF₃ OCH₃ H c-C₃H₅C₂H₄OCH₃ — 1655 O Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1656 O Cl COCH₃ H c-C₃H₅C₂H₄OCH₃ — 1657 O CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1658 O Cl CH₃ F c-C₃H₅C₂H₄OCH₃ — 1659 O CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1660 O CH₃ CH₃ CH₃ c-C₃H₅C₂H₄OCH₃ — 1661 O Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1662 O Cl OCH₃ H C₂H₅CH₂OCH₃ — 1663 O CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1664 O Cl SO₂CH₃ H C₂H₅CH₂OCH₃ — 1665 O Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1666 O CH₃ OCH₃ CH₃ C₂H₅CH₂OCH₃ — 1667 O Cl CH₃ F C₂H₅ CH₂OCH₃ — 1668 O CH₃ OCH₃ F C₂H₅ CH₂OCH₃— 1669 O CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1670 O Cl CF₃ H c-C₃H₅ CH₂OCH₃ —1671 O Cl Cl H c-C₃H₅ CH₂OCH₃ — 1672 O Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1673 OCF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1674 O Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1675 OCl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1676 O CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1677 OCl CH₃ F c-C₃H₅ CH₂OCH₃ — 1678 O CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1679 O CH₃CH₃ CH₃ c-C₃H₅ CH₂OCH₃ —

The methods discussed below in the preparation of1-benzyl-6-methyl-4-(2,4,6-trimethylphenyl)imidazo[4,5-c]pyridine(Example 2001, Table 2, Structure A) may be used to prepare all of theexamples of Structure A contained in Table 2, with minor proceduralmodifications where necessary and use of reagents of the appropriatestructure.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 2, with minorprocedural modifications where necessary and use of reagents of theappropriate structure.

EXAMPLE 2001 Preparation of1-Benzyl-6-methyl-4-(2,4,6-trimethylphenyl)imidazo[4,5-c]pyridine

Part A. A solution of 4-chloro-6-methyl-3-nitropyridone (5.0 g, 26.5mmol) in acetonitrile (93 mL) was treated with benzylamine (2.89 mL,26.5 mmol) and diisopropylethylamine (5.54 mL, 31.8 mmol). The mixturewas heated to reflux for 4 hrs., then cooled to ambient temperature andallowed to stir for 12 hrs. The mixture was partitioned betweendichloromethane and water (200 mL each), and the aqueous layer wasextracted with dichloromethane (200 mL). The extracts were washed insequence with water (200 mL) and combined, and the resulting precipitatewas collected by filtration. The filtrate was dried over sodium sulfate,refiltered and evaporated to afford a second crop of crystallineproduct, 4-benzylamino-6-methyl-3-nitropyridone (6.74 g total, 26.0mmol, 98%). m.p. 246-247° C. TLC R_(F) 0.35 (10:90 isopropanol-ethylacetate). ¹H NMR (300 MHz, CDCl₃): d 10.48 (1H, br s), 9.69 (1H, br s),7.41-7.26 (5H, m), 5.66 (1H, s), 4.57 (2H, d, J=5.5 Hz), 2.26 (3H, s).MS (NH₃—CI): m/e 261 (10), 260 (70), 226 (100).

Part B. A solution of the pyridone from Part A (6.72 g, 25.9 mmol) inphosphorus oxychloride (52 mL, 25.5 mmol) was stirred at ambienttemperature for 3 d. The reaction mixture was poured into a mixture ofice (150 g) and dichloromethane (200 mL). After the ice had melted, 100mL more dichloromethane was added, and the pH of the mixture wasadjusted to 7 with solid NaHCO₃. The mixture was separated, and theaqueous phase was extracted with dichloromethane. The extracts werecombined, dried over sodium sulfate, filtered and evaporated to affordthe product (4-benzylamino-2-chloro-6-methyl-3-nitropyridine) as abright yellow crystalline solid (6.45 g, 23.2 mmol, 90%). TLC R_(F) 0.76(ethyl acetate). ¹H NMR (300 MHz, CDCl₃): d 7.43-7.26 (5H, m), 7.04 (1H,br), 6.47 (1H, s), 4.48 (2H, d, J=5.5 Hz), 2.40 (3H, s). MS (NH₃—CI):m/e 281 (5), 280 (35), 279 (17), 278 (100).

Part C. A solution of the nitro compound from Part B above (6.42 g, 23.1mmol) in methanol (162 mL) was treated with iron powder (13.61 g) andglacial acetic acid (13.6 mL). The resulting mixture was heated toreflux for 2 h, then cooled, filtered through celite (with methanolwashing) and evaporated. The residual material was taken up indichloromethane (231 mL) and 1 N aq. HCl (162 mL), and adjusted toneutral pH by addition of solid NaHCO₃. This mixture was filteredthrough celite and separated, and the aqueous phase was extracted withdichloromethane. The extracts were combined, dried over Na₂SO₄, filteredand evaporated to afford the product,3-amino-4-benzylamino-2-chloro-6-methylpyridine, as a solid (5.59 g,22.6 mmol, 98%). m.p. 177-178° C. TLC R_(F) 0.60 (ethyl acetate). ¹H NMR(300 MHz, CDCl₃): d 7.41-7.32 (5H, m), 6.33 (1H, s), 4.54 (1H, br), 4.36(2H, d, J=5.1 Hz), 3.30 (2H, br s), 2.35 (3H, s). MS (NH₃—CI): m/e 251(6), 250 (37), 249 (19), 248 (100).

Part D. A suspension of the diamine from Part C above (2.15 g, 8.68mmol) in triethyl orthopropionate (5 mL) was treated with conc. HCl (3drops), and heated to reflux for 1 h, then cooled and the excessorthoester removed by vacuum distillation. The pot residue was taken upin ethyl acetate (120 mL), which was washed with water and brine (100 mLeach). The aqueous phases were back-extracted in sequence with ethylacetate, and the extracts were combined, dried over Na₂SO₄, filtered andevaporated to affordN-(4-benzylamino-2-chloro-6-methylpyridin-3-yl)propionamide O-ethylimidate (2.62 g, 91%). TLC R_(F) 0.40 (30:70 ethyl acetate-hexane). ¹HNMR (300 MHz, CDCl₃): d 7.39-7.29 (5H, m), 6.29 (1H, s), 4.64 (1H, br t,J=5.8 Hz), 4.37 (2H, d, J=5.8 Hz), 4.25 (2H, br), 2.35 (3H, s),2.18-2.11 (2H, m), 1.36 (3H, t, J=7.0 Hz), 1.06 (3H, t, J=7.7 Hz). MS(NH₃—CI): m/e 335 (7), 334 (34), 333 (22), 332 (100).

Part E. A solution of the compound from Part D (2.62 g, 7.90 mmol) inphenyl ether (10 mL) was heated to 170° C. for 6 h, then cooled andpoured into ethyl acetate (150 mL). This was washed with water and brine(100 mL each), then dried over Na₂SO₄, filtered and evaporated. Theresidual liquid was separated by column chromatography (hexane, thenethyl acetate) to afford the product,1-benzyl-4-chloro-2-ethyl-6-methylimidazo[4,5-c]pyridine, as an oil(2.16 g, 96 %). m.p. 140-141° C. TLC R_(F) 0.06 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.36-7.32 (3H, m), 7.02-6.98(2H, m), 6.93 (1H, s), 5.31 (2H, s), 2.89 (2H, q, J=7.3 Hz), 2.58 (3H,s), 1.39 (3H, t, J=7.3 Hz). MS (NH₃—CI): m/e 289 (6), 288 (35), 287(20), 286 (100).

Part F. A solution of zinc chloride (538 mg) in tetrahydrofuran (7 mL)was treated with a tetrahydrofuran solution of 2-mesitylmagnesiumbromide (3.95 mL, 1.0 M), and stirred for 1 h. In another flask, asolution of bis(triphenylphosphine)palladium chloride (93 mg, 0.132mmol) in tetrahydrofuran (5 mL) was treated with a hexane solution ofdiisobutylaluminum hydride (0.263 mL, 1.0 M), and this solution wasstirred for 20 min. The arylzinc solution was then delivered by cannulato the flask containing the palladium catalyst, which was followed bythe chloride prepared in Part E. The mixture was heated to reflux for 12h, then cooled, and poured into water (100 mL). This was extracted withethyl acetate (2×150 mL), and the extracts were washed with brine,combined, dried over Na₂SO₄, filtered and evaporated. The residualmaterial was separated by column chromatography (1:1 ethylacetate-hexane) to afford the title product as a solid, recrystallizedto purity from ether (187 mg, 29%). m.p. 177-180° C. (ether). TLC R_(F)0.27 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.38-7.32(3H, m), 7.10-7.05 (2H, m), 6.96 (1H, s), 6.93 (2H, s), 5.32 (2H, s),2.84 (2H, q, J=7.3 Hz), 2.64 (3H, s), 2.30 (3H, s), 2.02 (6H, s), 1.26(3H, t, J=7.3 Hz). MS (NH₃CI): m/e 372 (4), 371 (29), 370 (100).Analysis calc'd for C₂5H₂₇N₃: C, 81.26; H, 7.38; N, 11.37; found: C,80.70; H, 7.26; N, 11.20.

TABLE 2

(A) (B)

(C) Ex. mp, No. X R⁴ R⁵ R¹¹ R⁶ R¹ ° C.^(a) 2001 CH₂ Cl Cl H H c-C₄H₇ —2002 CH₂ Cl Cl H H c-C₅H₉ 111-112 2003 CH₂ Cl Cl H H c-C₆H₁₁ oil 2004CH₂ Cl Cl H H c-C₇H₁₃ 128-130 2005 CH₂ Cl Cl H H c-C₈H₁₅ — 2006 CH₂ ClCl H H 2-CH₃-c-C₅H₈ oil 2007 CH₂ Cl Cl H H 3-CH₃-c-C₅H₈ — 2008 CH₂ Cl ClH H 2-OCH₃-c-C₅H₈ — 2009 CH₂ Cl Cl H H 2,5-(CH₃)₂-c-C₅H₇ — 2010 CH₂ ClCl H H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2011 CH₂ Cl Cl H H 9-fluorenyl oil 2012CH₂ Cl Cl H H 1-tetrahydronaphthyl oil 2013 CH₂ Cl Cl H H 1-indanyl oil2014 CH₂ Cl Cl H H 4-chromanyl oil 2015 CH₂ Cl Cl H H 2-oxo-c-C₅H₇166-168 2016 CH₂ Cl Cl H H 5-dibenzosuberyl — 2017 CH₂ Cl Cl H H5-dibenzosuberenyl — 2018 CH₂ Cl CF₃ H H c-C₄H₇ — 2019 CH₂ Cl CF₃ H Hc-C₅H₉ 146-147 2020 CH₂ Cl CF₃ H H c-C₆H₁₁ oil 2021 CH₂ Cl CF₃ H Hc-C₇H₁₃ 129-130 2022 CH₂ Cl CF₃ H H c-C₈H₁₅ — 2023 CH₂ Cl CF₃ H H2-CH₃-c-C₅H₈ 98-99 2024 CH₂ Cl CF₃ H H 3-CH₃-c-C₅H₈ — 2025 CH₂ Cl CF₃ HH 2-OCH₃-c-C₅H₈ — 2026 CH₂ Cl CF₃ H H 2,5-(CH₃)₂-c-C₅H₇ — 2027 CH₂ ClCF₃ H H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2028 CH₂ Cl CF₃ H H 9-fluorenyl — 2029CH₂ Cl CF₃ H H 1-tetrahydronaphthyl — 2030 CH₂ Cl CF₃ H H 1-indanyl —2031 CH₂ Cl CF₃ H H 4-chromanyl — 2032 CH₂ Cl CF₃ H H 2-oxo-c-C₅H₇ —2033 CH₂ Cl CF₃ H H 5-dibenzosuberyl — 2034 CH₂ Cl CF₃ H H5-dibenzosuberenyl — 2035 CH₂ Cl OCH₃ H H c-C₄H₇ — 2036 CH₂ Cl OCH₃ H Hc-C₅H₉ — 2037 CH₂ Cl OCH₃ H H c-C₆H₁₁ — 2038 CH₂ Cl OCH₃ H H c-C₇H₁₃ —2039 CH₂ Cl OCH₃ H H c-C₈H₁₅ — 2040 CH₂ Cl OCH₃ H H 2-CH₃-c-C₅H₈ — 2041CH₂ Cl OCH₃ H H 3-CH₃-c-C₅H₈ — 2042 CH₂ Cl OCH₃ H H 2-OCH₃-c-C₅H₈ — 2043CH₂ Cl OCH₃ H H 2,5-(CH₃)₂-c-C₅H₇ — 2044 CH₂ Cl OCH₃ H H2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2045 CH₂ Cl OCH₃ H H 9-fluorenyl — 2046 CH₂ ClOCH₃ H H 1-tetrahydronaphthyl — 2047 CH₂ Cl OCH₃ H H 1-indanyl — 2048CH₂ Cl OCH₃ H H 4-chromanyl — 2049 CH₂ Cl OCH₃ H H 2-oxo-c-C₅H₇ — 2050CH₂ Cl OCH₃ H H 5-dibenzosuberyl — 2051 CH₂ Cl OCH₃ H H5-dibenzosuberenyl — 2052 CH₂ Cl OCF₃ H H c-C₄H₇ — 2053 CH₂ Cl OCF₃ H Hc-C₅H₉ oil 2054 CH₂ Cl OCF₃ H H c-C₆H₁₁ — 2055 CH₂ Cl OCF₃ H H c-C₇H₁₃ —2056 CH₂ Cl OCF₃ H H c-C₈H₁₅ — 2057 CH₂ Cl OCF₃ H H 2-CH₃-c-C₅H₈ — 2058CH₂ Cl OCF₃ H H 3-CH₃-c-C₅H₈ — 2059 CH₂ Cl OCF₃ H H 2-OCH₃-c-C₅H₈ — 2060CH₂ Cl OCF₃ H H 2,5-(CH₃)₂-c-C₅H₇ — 2061 CH₂ Cl OCF₃ H H2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2062 CH₂ Cl OCF₃ H H 9-fluorenyl — 2063 CH₂ ClOCF₃ H H 1-tetrahydronaphthyl — 2064 CH₂ Cl OCF₃ H H 1-indanyl — 2065CH₂ Cl OCF₃ H H 4-chromanyl — 2066 CH₂ Cl OCF₃ H H 2-oxo-c-C₅H₇ — 2067CH₂ Cl OCF₃ H H 5-dibenzosuberyl — 2068 CH₂ Cl OCF₃ H H5-dibenzosuberenyl — 2069 CH₂ Cl CH₃ H H c-C₄H₇ — 2070 CH₂ Cl CH₃ H Hc-C₅H₉ — 2071 CH₂ Cl CH₃ H H c-C₆H₁₁ — 2072 CH₂ Cl CH₃ H H c-C₇H₁₃ —2073 CH₂ Cl CH₃ H H c-C₈H₁₅ — 2074 CH₂ Cl CH₃ H H 2-CH₃-c-C₅H₈ — 2075CH₂ Cl CH₃ H H 3-CH₃-c-C₅H₈ — 2076 CH₂ Cl CH₃ H H 2-OCH₃-c-C₅H₈ — 2077CH₂ Cl CH₃ H H 2,5-(CH₃)₂-c-C₅H₇ — 2078 CH₂ Cl CH₃ H H2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2079 CH₂ Cl CH₃ H H 9-fluorenyl — 2080 CH₂ ClCH₃ H H 1-tetrahydronaphthyl — 2081 CH₂ Cl CH₃ H H 1-indanyl — 2082 CH₂Cl CH₃ H H 4-chromanyl — 2083 CH₂ Cl CH₃ H H 2-oxo-c-C₅H₇ — 2084 CH₂ ClCH₃ H H 5-dibenzosuberyl — 2085 CH₂ Cl CH₃ H H 5-dibenzosuberenyl — 2086CH₂ CF₃ Cl H H c-C₄H₇ — 2087 CH₂ CF₃ Cl H H c-C₅H₉ 143-145 2088 CH₂ CF₃Cl H H c-C₆H₁₁ — 2089 CH₂ CF₃ Cl H H c-C₇H₁₃ — 2090 CH₂ CF₃ Cl H Hc-C₈H₁₅ — 2091 CH₂ CF₃ Cl H H 2-CH₃-c-C₅H₈ — 2092 CH₂ CF₃ Cl H H3-CH₃-c-C₅H₈ — 2093 CH₂ CF₃ Cl H H 2-OCH₃-c-C₅H₈ — 2094 CH₂ CF₃ Cl H H2,5-(CH₃)₂-c-C₅H₇ — 2095 CH₂ CF₃ Cl H H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2096CH₂ CF₃ Cl H H 9-fluorenyl — 2097 CH₂ CF₃ Cl H H 1-tetrahydronaphthyl —2098 CH₂ CF₃ Cl H H 1-indanyl — 2099 CH₂ CF₃ Cl H H 4-chromanyl — 2100CH₂ CF₃ Cl H H 2-oxo-c-C₅H₇ — 2101 CH₂ CF₃ Cl H H 5-dibenzosuberyl —2102 CH₂ CF₃ Cl H H 5-dibenzosuberenyl — 2103 CH₂ CF₃ OCH₃ H H c-C₄H₇ —2104 CH₂ CF₃ OCH₃ H H c-C₅H₉ 103-106 2105 CH₂ CF₃ OCH₃ H H c-C₆H₁₁ —2106 CH₂ CF₃ OCH₃ H H c-C₇H₁₃ — 2107 CH₂ CF₃ OCH₃ H H c-C₈H₁₅ — 2108 CH₂CF₃ OCH₃ H H 2-CH₃-c-C₅H₈ — 2109 CH₂ CF₃ OCH₃ H H 3-CH₃-c-C₅H₈ — 2110CH₂ CF₃ OCH₃ H H 2-OCH₃-c-C₅H₈ — 2111 CH₂ CF₃ OCH₃ H H 2,5-(CH₃)₂-c-C₅H₇— 2112 CH₂ CF₃ OCH₃ H H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2113 CH₂ CF₃ OCH₃ H H9-fluorenyl — 2114 CH₂ CF₃ OCH₃ H H 1-tetrahydronaphthyl — 2115 CH₂ CF₃OCH₃ H H 1-indanyl — 2116 CH₂ CF₃ OCH₃ H H 4-chromanyl — 2117 CH₂ CF₃OCH₃ H H 2-oxo-c-C₅H₇ — 2118 CH₂ CF₃ OCH₃ H H 5-dibenzosuberyl — 2119CH₂ CF₃ OCH₃ H H 5-dibenzosuberenyl — 2120 CH₂ CF₃ F H H c-C₄H₇ — 2121CH₂ CF₃ F H H c-C₅H₉ — 2122 CH₂ CF₃ F H H c-C₆H₁₁ — 2123 CH₂ CF₃ F H Hc-C₇H₁₃ 119-122 2124 CH₂ CF₃ F H H c-C₈H₁₅ — 2125 CH₂ CF₃ F H H2-CH₃-c-C₅H₈ — 2126 CH₂ CF₃ F H H 3-CH₃-c-C₅H₈ — 2127 CH₂ CF₃ F H H2-OCH₃-c-C₅H₈ — 2128 CH₂ CF₃ F H H 2,5-(CH₃)₂-c-C₅H₇ — 2129 CH₂ CF₃ F HH 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ 155-156 2130 CH₂ CF₃ F H H 9-fluorenyl 184-1852131 CH₂ CF₃ F H H 1-tetrahydronaphthyl — 2132 CH₂ CF₃ F H H 1-indanyl —2133 CH₂ CF₃ F H H 4-chromanyl — 2134 CH₂ CF₃ F H H 2-oxo-c-C₅H₇ — 2135CH₂ CF₃ F H H 5-dibenzosuberyl — 2136 CH₂ CF₃ F H H 5-dibenzosuberenyl —2137 CH₂ CH₃ OCH₃ CH₃ H c-C₄H₇ — 2138 CH₂ CH₃ OCH₃ CH₃ H c-C₅H₉ — 2139CH₂ CH₃ OCH₃ CH₃ H c-C₆H₁₁ — 2140 CH₂ CH₃ OCH₃ CH₃ H c-C₇H₁₃ — 2141 CH₂CH₃ OCH₃ CH₃ H c-C₈H₁₅ — 2142 CH₂ CH₃ OCH₃ CH₃ H 2-CH₃-c-C₅H₈ — 2143 CH₂CH₃ OCH₃ CH₃ H 3-CH₃-c-C₅H₈ — 2144 CH₂ CH₃ OCH₃ CH₃ H 2-OCH₃-c-C₅H₈ —2145 CH₂ CH₃ OCH₃ CH₃ H 2,5-(CH₃)₂-c-C₅H₇ — 2146 CH₂ CH₃ OCH₃ CH₃ H2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2147 CH₂ CH₃ OCH₃ CH₃ H 9-fluorenyl — 2148 CH₂CH₃ OCH₃ CH₃ H 1-tetrahydronaphthyl — 2149 CH₂ CH₃ OCH₃ CH₃ H 1-indanyl— 2150 CH₂ CH₃ OCH₃ CH₃ H 4-chromanyl — 2151 CH₂ CH₃ OCH₃ CH₃ H2-oxo-c-C₅H₇ — 2152 CH₂ CH₃ OCH₃ CH₃ H 5-dibenzosuberyl — 2153 CH₂ CH₃OCH₃ CH₃ H 5-dibenzosuberenyl — 2154 CH₂ CH₃ OCH₃ Cl H c-C₄H₇ — 2155 CH₂CH₃ OCH₃ Cl H c-C₅H₉ 115-116 2156 CH₂ CH₃ OCH₃ Cl H c-C₆H₁₁ — 2157 CH₂CH₃ OCH₃ Cl H c-C₇H₁₃ — 2158 CH₂ CH₃ OCH₃ Cl H c-C₈H₁₅ — 2159 CH₂ CH₃OCH₃ Cl H 2-CH₃-c-C₅H₈ — 2160 CH₂ CH₃ OCH₃ Cl H 3-CH₃-c-C₅H₈ — 2161 CH₂CH₃ OCH₃ Cl H 2-OCH₃-c-C₅H₈ — 2162 CH₂ CH₃ OCH₃ Cl H 2,5-(CH₃)₂-c-C₅H₇ —2163 CH₂ CH₃ OCH₃ Cl H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2164 CH₂ CH₃ OCH₃ Cl H9-fluorenyl — 2165 CH₂ CH₃ OCH₃ Cl H 1-tetrahydronaphthyl — 2166 CH₂ CH₃OCH₃ Cl H 1-indanyl — 2167 CH₂ CH₃ OCH₃ Cl H 4-chromanyl — 2168 CH₂ CH₃OCH₃ Cl H 2-oxo-c-C₅H₇ — 2169 CH₂ CH₃ OCH₃ Cl H 5-dibenzosuberyl — 2170CH₂ CH₃ OCH₃ Cl H 5-dibenzosuberenyl — 2171 CH₂ CH₃ OCH₃ F H c-C₄H₇ —2172 CH₂ CH₃ OCH₃ F H c-C₅H₉ — 2173 CH₂ CH₃ OCH₃ F H c-C₆H₁₁ — 2174 CH₂CH₃ OCH₃ F H c-C₇H₁₃ — 2175 CH₂ CH₃ OCH₃ F H c-C₈H₁₅ — 2176 CH₂ CH₃ OCH₃F H 2-CH₃-c-C₅H₈ — 2177 CH₂ CH₃ OCH₃ F H 3-CH₃-c-C₅H₈ — 2178 CH₂ CH₃OCH₃ F H 2-OCH₃-c-C₅H₈ — 2179 CH₂ CH₃ OCH₃ F H 2,5-(CH₃)₂-c-C₅H₇ — 2180CH₂ CH₃ OCH₃ F H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2181 CH₂ CH₃ OCH₃ F H9-fluorenyl — 2182 CH₂ CH₃ OCH₃ F H 1-tetrahydronaphthyl — 2183 CH₂ CH₃OCH₃ F H 1-indanyl — 2184 CH₂ CH₃ OCH₃ F H 4-chromanyl — 2185 CH₂ CH₃OCH₃ F H 2-oxo-c-C₅H₇ — 2186 CH₂ CH₃ OCH₃ F H 5-dibenzosuberyl — 2187CH₂ CH₃ OCH₃ F H 5-dibenzosuberenyl — 2188 CH₂ CH₃ CH₃ H CH₃ c-C₄H₇ —2189 CH₂ CH₃ CH₃ H CH₃ c-C₅H₉ — 2190 CH₂ CH₃ CH₃ H CH₃ c-C₆H₁₁ — 2191CH₂ CH₃ CH₃ H CH₃ c-C₇H₁₃ — 2192 CH₂ CH₃ CH₃ H CH₃ c-C₈H₁₅ — 2193 CH₂CH₃ CH₃ H CH₃ 2-CH₃-c-C₅H₈ — 2194 CH₂ CH₃ CH₃ H CH₃ 3-CH₃-c-C₅H₈ — 2195CH₂ CH₃ CH₃ H CH₃ 2-OCH₃-c-C₅H₈ — 2196 CH₂ CH₃ CH₃ H CH₃2,5-(CH₃)₂-c-C₅H₇ — 2197 CH₂ CH₃ CH₃ H CH₃ 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ —2198 CH₂ CH₃ CH₃ H CH₃ 9-fluorenyl — 2199 CH₂ CH₃ CH₃ H CH₃1-tetrahydronaphthyl — 2200 CH₂ CH₃ CH₃ H CH₃ 1-indanyl — 2201 CH₂ CH₃CH₃ H CH₃ 4-chromanyl — 2202 CH₂ CH₃ CH₃ H CH₃ 2-oxo-c-C₅H₇ — 2203 CH₂CH₃ CH₃ H CH₃ 5-dibenzosuberyl — 2204 CH₂ CH₃ CH₃ H CH₃5-dibenzosuberenyl — 2205 CH₂ Cl Cl H CH₃ c-C₄H₇ — 2206 CH₂ Cl Cl H CH₃c-C₅H₉ — 2207 CH₂ Cl Cl H CH₃ c-C₆H₁₁ — 2208 CH₂ Cl Cl H CH₃ c-C₇H₁₃ —2209 CH₂ Cl Cl H CH₃ c-C₈H₁₅ — 2210 CH₂ Cl Cl H CH₃ 2-CH₃-c-C₅H₈ — 2211CH₂ Cl Cl H CH₃ 3-CH₃-c-C₅H₈ — 2212 CH₂ Cl Cl H CH₃ 2-OCH₃-c-C₅H₈ — 2213CH₂ Cl Cl H CH₃ 2,5-(CH₃)₂-c-C₅H₇ — 2214 CH₂ Cl Cl H CH₃2-(CH₃)₂CH-5-CH₃-c-C₆H₉ — 2215 CH₂ Cl Cl H CH₃ 9-fluorenyl — 2216 CH₂ ClCl H CH₃ 1-tetrahydronaphthyl oil 2217 CH₂ Cl Cl H CH₃ 1-indanyl — 2218CH₂ Cl Cl H CH₃ 4-chromanyl — 2219 CH₂ Cl Cl H CH₃ 2-oxo-c-C₅H₇ — 2220CH₂ Cl Cl H CH₃ 5-dibenzosuberyl — 2221 CH₂ Cl Cl H CH₃5-dibenzosuberenyl — 2222 CH₂ CH₃ OCH₃ OCH₃ H c-C₄H₇ — 2223 CH₂ CH₃ OCH₃OCH₃ H c-C₅H₉ oil 2224 CH₂ CH₃ OCH₃ OCH₃ H c-C₆H₁₁ — 2225 CH₂ CH₃ OCH₃OCH₃ H c-C₇H₁₃ — 2226 CH₂ CH₃ OCH₃ OCH₃ H c-C₈H₁₅ — 2227 CH₂ CH₃ OCH₃OCH₃ H 2-CH₃-c-C₅H₈ oil 2228 CH₂ CH₃ OCH₃ OCH₃ H 3-CH₃-c-C₅H₈ — 2229 CH₂CH₃ OCH₃ OCH₃ H 2-OCH₃-c-C₅H₈ — 2230 CH₂ CH₃ OCH₃ OCH₃ H2,5-(CH₃)₂-c-C₅H₇ — 2231 CH₂ CH₃ OCH₃ OCH₃ H 2-(CH₃)₂CH-5-CH₃-c-C₆H₉ —2232 CH₂ CH₃ OCH₃ OCH₃ H 9-fluorenyl — 2233 CH₂ CH₃ OCH₃ OCH₃ H1-tetrahydronaphthyl — 2234 CH₂ CH₃ OCH₃ OCH₃ H 1-indanyl — 2235 CH₂ CH₃OCH₃ OCH₃ H 4-chromanyl — 2236 CH₂ CH₃ OCH₃ OCH₃ H 2-oxo-c-C₅H₇ — 2237CH₂ CH₃ OCH₃ OCH₃ H 5-dibenzosuberyl — 2238 CH₂ CH₃ OCH₃ OCH₃ H5-dibenzosuberenyl — 2239 O Cl Cl H H c-C₅H₉ — 2240 O Cl CF₃ H H c-C₅H₉— 2241 O Cl OCH₃ H H c-C₅H₉ — 2242 O Cl OCF₃ H H c-C₅H₉ — 2243 O Cl CH₃H H c-C₅H₉ — 2244 O CF₃ Cl H H c-C₅H₉ — 2245 O CF₃ OCH₃ H H c-C₅H₉ —2246 O CH₃ OCH₃ CH₃ H c-C₅H₉ — 2247 O CH₃ OCH₃ Cl H c-C₅H₉ — 2248 O CH₃OCH₃ F H c-C₅H₉ — 2249 O CH₃ CH₃ H CH₃ c-C₅H₉ — 2250 O Cl Cl H CH₃c-C₅H₉ — Key: ^(a)Where the compound is listed as an “oil”, spectraldata is as follows: Example 2003 spectral data: MS(NH₃—CI): m/e 374(M +H⁺, 100%). Example 2006 spectral data: TLC R_(F) 0.20(20:80 ethylacetate-hexane). ¹H NMR(300 MHz, CDCl₃): δ 8.94(1H, s), 7.67(1H, d,J=8.1Hz), 7.57(1H, d, J=1.8Hz), 7.40(1H, dd, J=8.1, 1.8Hz), 4.83(1H, q,J=8.0Hz), 3.20-3.04(1H, m), 2.98(2H, q, J=7.3Hz), 2.50-2.38(1H, m),2.30-2.15(2H, m), 2.03-1.93(2H, m), 1.75-1.60(1H, m), # 1.42(3H, t,J=7.3Hz), 0.68(3H, d, J=6.9Hz). MS(NH₃—CI): m/e calc'd for C₁₉H₂₁Cl₂N₄:375.1143, found 375.1149; 380(2), 379(12), 378(15), 377(66), 376(27),375(100). Example 2011 spectral data: MS(NH₃—CI): m/e 457(M+H⁺, 100%).Example 2012 spectral data: TLC R_(F) 0.38(30:70 ethyl acetate-hexane).¹H NMR(300 MHz, CDCl₃): δ 8.94(1H, s), 7.72(1H, d, J=8.5Hz), 7.58(1H, d,J=1.8Hz), 7.47-7.40(2H, m), 7.24-7.18(1H, m), 6.56(1H, d, J=7.7Hz),6.18-6.10(1H, m), 4.82-4.76(1H, m), 3.15-2.30(5H, m), 2.10-1.77(3H, m),1.27(3H, t, J=7.5Hz). MS(NH₃—CI): # m/e calc'd for C₂₃H₂₁Cl₂N₄:423.1143, found 423.1142; 427(13), 426(18), 425(67), 424(31), 423(100).Example 2013 spectral data: TLC R_(F) 0.28(30:70 ethyl acetate-hexane).¹H NMR(300MHz, CDCl₃): δ 8.91(1H, s), 7.68(1H, d, J=8.5Hz), 7.58(1H, d,J=1.8Hz), 7.46-7.38(2H, m), 7.22-7.15(1H, m), 6.91(1H, d, J=7.7Hz),6.42(1H, br t, J=7Hz), 5.30-5.22(1H, m), 3.43-3.33(1H, m), 3.20-3.03(1H,m), 2.89-2.76(2H, m), 2.56-2.43(1H, m), 2.01-1.90 #(1H, m), 1.31(3H, t,J=7.5Hz). MS(NH₃—CI): m/e calc'd for C₂₂H₁₉Cl₂N₄: 409.0987, found409.0987; 413(12), 412(17), 411(67), 410(29), 409(100). Example 2014spectral data: TLC R_(F) 0.38(30:70 ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ 8.95(1H, s), 7.71(1H, d, J=8.4Hz), 7.59(1H, d, J=2.2Hz),7.42(1H, dd, J=8.4, 2.2Hz), 7.26-7.19(1H, m), 6.98-6.90(1H, m), 6.58(1H,d, J=7.7Hz), 6.30-6.22(1H, m), 4.60-4.53(1H, m), 4.43-4.33(1H, m),4.20(1H, br), 2.82-2.72(1H, m), 2.69-2.58 #(1H, m), 2.46-2.36(1H, m),2.18-2.08(1H, m), 1.29(3H, t, J=7.5Hz). MS(NH₃—CI): m/e calc'd forC₂₂H₁₉Cl₂N₄O: 425.0936, found 425.0926; 429(12), 428(17), 427(67),426(30), 425(100). Example 2020 spectral data: TLC R_(F) 0.43(30:70ethyl acetate-hexane). ¹H NMR(300MHz, CDCl₃): δ 8.98(1H, s), 7.81(2H, d,J=8.4Hz), 7.67(1H, dd, J=8.0, 0.7Hz), 4.26(1H, m), 3.00(2H, q, J=7.6Hz),2.75-2.66(2H, m), 2.06-1.90(4H, m), 1.50-1.36(4H, m), 1.40(3H, t,J=7.5Hz). MS(NH₃—CI): m/e 412(7), 411(34), 410(25), 409(100). Example2053 spectral data: TLC R_(F) 0.36(25:75 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ 8.96(1H, s), 7.73(1H, d, J=8.4Hz), 7.44(1H, d,J=1.1Hz), 7.28(1H, dd, J=8.4, 1.1hz), 4.79(1H, pentet, J=8.4Hz),3.01(2H, q, J=7.7Hz), 2.62-2.50(2H, m), 2.23-2.07(2H, m), 1.89-1.77(2H,m), 1.66-1.49(2H, m), 1.41(3H, t, J=7.7Hz). MS(NH₃—CI): # m/e calculatedfor C₁₉H₁₉ClF₃N₄O: 411.1205, found 411.1208; 414(7), 413(34), 412(24),411(100). Example 2216 spectral data: TLC R_(F) 0.13(20:80 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ 8.94(1H, s), 7.48-7.02(5H, m),6.53(1H, dd, J=7.7, 1.5Hz), 6.18-6.10(1H, m), 3.16-2.20(5H, m), 2.13(3H,d, J=4.8Hz), 2.06-1.70(3H, m), 1.23(3H, dt, J=7.4, 4.4Hz). MS(NH³—CI):m/e calc'd for C₂₄H₂₃Cl₂N₄: # 437.1300, found 437.1299; 439(67),437(100). Example 2223 spectral data: TLC R_(F) 0.36(50:50 ethylacetate-hexane). ¹H NMR(300MHz, CDCl₃): δ 8.91(1H, s), 7.33(1H, s),6.83(1H, s), 4.78(1H, pentet, J=8.5Hz), 3.94(3H, s), 3.90(3H, s),2.98(2H, q, J=7.6Hz), 2.58-2.48(2H, m), 2.42(3H, s), 2.19-2.07(2H, m),1.84-1.56(4H, m), 1.43(3H, t, J=7.5Hz). MS(NH₃—CI): # m/e calc'd forC₂₁H₂₇N₄O₂: 367.2134, found 367.2120; 369(3), 368(24), 367(100). Example2227 spectral data: TLC R_(F) 0.45(50:50 ethyl acetate-hexane). ¹HNMR(300MHz, CDCl₃): δ 8.90(1H, s), 7.37(1H, s), 6.83(1H, s), 4.85(1H, q,J=8.4Hz), 3.94(3H, s), 3.91(3H, s), 3.19-3.11(1H, m), 2.96(2H, dq,J=7.9, 1.5Hz), 2.41(3H, s), 2.24-2.16(2H, m), 2.04-1.94(2H, m),1.71-1.62(2H, m), 1.44(3H, t, J=7.4Hz), 0.69(3H, d, J=6.9Hz). #MS(NH₃—CI): m/e calc'd for C₂₂H₂₉N₄O₂: 381.2290, found 381.2294; 383(4),382(25), 381(100).

The methods discussed below in the preparation of3-benzyl-5-methyl-7-(2,4, 6-trimethylphenyl)-imidazo[4,5-b]pyridine(Example 3001, Table 3) may be used to prepare all of the examples ofStructure A contained in Table 3, with minor procedural modificationswhere necessary and use of reagents of the appropriate structure.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 3, with minorprocedural modifications where necessary and use of reagents of theappropriate structure.

EXAMPLE 3001 Preparation of3-Benzyl-5-methyl-7-(2,4,6-trimethylphenyl)imidazo[4,5-b]pyridine

Part A. A solution of 2,4,6-trimethylbenzeneboronic acid in benzene (0.5M) is treated with excess n-butanol, and the solution is heated toreflux under a Dean-Stark still head to azeotropically remove water.Solvent is removed by evaporation, and the resulting dibutyl2,4,6-trimethylbenzeneboronate is used directly in Part B.

Part B. The method of Snieckus et al. (Fu, J. M.; Zhao, B. P.; Sharp, M.J.; Snieckus, V. Can. J. Chem. 1994, 72, 227-236) may be employed here.Thus, a solution of 4-chloro-6-methyl-3-nitro-2-pyridone indimethylformamide (0.1 M) is treated with the boronate from Part A (1.2eq), tribasic potassium phosphate (2.4 eq), and[1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium (0.1 eq). Themixture is stirred at ambient temperature for 30 hrs., then poured into4 volumes ethyl acetate. This is washed with 3 equal volumes of water,then brine. The extract is dried over Na₂SO₄, filtered and evaporated.Chromatographic separation affords pure6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)-2-pyridone.

Part C. The pyridone from Part B is suspended in 6 eq phosphorusoxychloride, and stirred with mild heating until the compound dissolves.The mixture is cooled, and poured over ice. After melting, the mixtureis extracted twice with dichloromethane, and the extracts are combined,dried over Na₂SO₄, filtered and evaporated. The product,2-chloro-6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)pyridine, is purifiedby either chromatography or recrystallization.

Part D. The chloride from Part C is dissolved in ethanol, and treatedwith benzylamine (1.2 eq.). The mixture is heated to reflux until thestarting material is consumed as determined by thin-layerchromatography. The mixture is evaporated, and the residual material ispartitioned between water and ethyl acetate. The organic layer isseparated, washed with brine, dried over Na₂SO₄, filtered andevaporated. The product,2-benzylamino-6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)pyridine, ispurified by either chromatography or recrystallization.

Part E. The nitro compound from Part D is dissolved in 1:1 aqueousdioxane, and treated with conc. aq. ammonium hydroxide solution. To thisis added solid sodium dithionite in several portions over 2 h. Themixture is allowed to stir for an additional 4 h, then partitionedbetween water and ethyl acetate. The organic layer is separated, washedwith brine, dried over Na₂SO₄, filtered and evaporated. The product,3-amino-2-benzylamino-6-methyl-4-(2,4,6-trimethylphenyl)pyridine, ispurified by either chromatography or recrystallization.

Part F. A suspension of the diamine from Part E above in triethylorthopropionate is treated with conc. HCl, and heated to reflux for 1 h,then cooled and the excess orthoester removed by vacuum distillation.The pot residue contains sufficiently pureN-[2-benzylamino-4-(2,4,6-trimethylphenyl)-6-methylpyridin-3-yl]propionamideO-ethyl imidate.

Part G. A solution of the compound from Part F in phenyl ether istreated with a catalytic amount of p-toluenesulfonic acid and heated to170° C. for 6 h, then cooled. The residual liquid is separated by columnchromatography (hexane, then ethyl acetate) to afford the title product.

TABLE 3

(A) (B)

(C) Ex. mp, No. X R⁴ R⁵ R¹¹ R⁶ R¹ ° C.^(a) 3001 CH₂ Cl Cl H H C(═O)OC₂H₅— 3002 CH₂ Cl Cl H H C(═O)OC₃H₇ 90-91 3003 CH₂ Cl Cl H H C(═O)OC₄H₉57-59 3004 CH₂ Cl Cl H H C(═O)OCH(CH₃)₂ 80-81 3005 CH₂ Cl Cl H HC(═O)OCH₂CH(CH₃)₂ 60-62 3006 CH₂ Cl Cl H H C(═O)N(CH₃)₂ — 3007 CH₂ Cl ClH H C(═O)N(C₂H₅)₂ 120-123 3008 CH₂ Cl Cl H H C(═O)N[CH(CH₃)₂]₂ 147-1493009 CH₂ Cl Cl H H C(═O)(1-morpholinyl) 158-159 3010 CH₂ Cl Cl H HSO₂C₆H₅ 132-133 3011 CH₂ Cl Cl H H SO₂(4-CH₃—C₆H₄) 154-155 3012 CH₂ ClCl H H SO₂(4-OCH₃—C₆H₄) 156-158 3013 CH₂ Cl Cl H H SO₂-(2-thienyl)176-178 3014 CH₂ Cl Cl H H SO₂CH₂C₆H₅ 127-129 3015 CH₂ Cl Cl H H SO₂C₃H₇100-101 3016 CH₂ Cl Cl H H SO₂C₄H₉ 79-80 3017 CH₂ Cl Cl H HC(═O)-(2-Cl—C₆H₄) 110-113 3018 CH₂ Cl CF₃ H H C(═O)OC₂H₅ — 3019 CH₂ ClCF₃ H H C(═O)OC₃H₇ — 3020 CH₂ Cl CF₃ H H C(═O)OC₄H₉ — 3021 CH₂ Cl CF₃ HH C(═O)OCH(CH₃)₂ — 3022 CH₂ Cl CF₃ H H C(═O)OCH₂CH(CH₃)₂ — 3023 CH₂ ClCF₃ H H C(═O)N(CH₃)₂ — 3024 CH₂ Cl CF₃ H H C(═O)N(C₂H₅)₂ — 3025 CH₂ ClCF₃ H H C(═O)N[CH(CH₃)₂]₂ — 3026 CH₂ Cl CF₃ H H C(═O)(1-morpholinyl) —3027 CH₂ Cl CF₃ H H SO₂C₆H₅ — 3028 CH₂ Cl CF₃ H H SO₂(4-CH₃—C₆H₄) — 3029CH₂ Cl CF₃ H H SO₂(4-OCH₃—C₆H₄) — 3030 CH₂ Cl CF₃ H H SO₂-(2-thienyl) —3031 CH₂ Cl CF₃ H H SO₂CH₂C₆H₅ — 3032 CH₂ Cl CF₃ H H SO₂C₃H₇ — 3033 CH₂Cl CF₃ H H SO₂C₄H₉ — 3034 CH₂ Cl CF₃ H H C(═O)-(2-Cl—C₆H₄) — 3035 CH₂ ClOCH₃ H H C(═O)OC₂H₅ — 3036 CH₂ Cl OCH₃ H H C(═O)OC₃H₇ — 3037 CH₂ Cl OCH₃H H C(═O)OC₄H₉ — 3038 CH₂ Cl OCH₃ H H C(═O)OCH(CH₃)₂ — 3039 CH₂ Cl OCH₃H H C(═O)OCH₂CH(CH₃)₂ — 3040 CH₂ Cl OCH₃ H H C(═O)N(CH₃)₂ — 3041 CH₂ ClOCH₃ H H C(═O)N(C₂H₅)₂ — 3042 CH₂ Cl OCH₃ H H C(═O)N[CH(CH₃)₂]₂ — 3043CH₂ Cl OCH₃ H H C(═O)(1-morpholinyl) — 3044 CH₂ Cl OCH₃ H H SO₂C₆H₅ —3045 CH₂ Cl OCH₃ H H SO₂(4-CH₃—C₆H₄) — 3046 CH₂ Cl OCH₃ H HSO₂(4-OCH₃—C₆H₄) — 3047 CH₂ Cl OCH₃ H H SO₂-(2-thienyl) — 3048 CH₂ ClOCH₃ H H SO₂CH₂C₆H₅ — 3049 CH₂ Cl OCH₃ H H SO₂C₃H₇ — 3050 CH₂ Cl OCH₃ HH SO₂C₄H₉ — 3051 CH₂ Cl OCH₃ H H C(═O)-(2-Cl—C₆H₄) — 3052 CH₂ Cl OCF₃ HH C(═O)OC₂H₅ — 3053 CH₂ Cl OCF₃ H H C(═O)OC₃H₇ — 3054 CH₂ Cl OCF₃ H HC(═O)OC₄H₉ — 3055 CH₂ Cl OCF₃ H H C(═O)OCH(CH₃)₂ — 3056 CH₂ Cl OCF₃ H HC(═O)OCH₂CH(CH₃)₂ — 3057 CH₂ Cl OCF₃ H H C(═O)N(CH₃)₂ — 3058 CH₂ Cl OCF₃H H C(═O)N(C₂H₅)₂ — 3059 CH₂ Cl OCF₃ H H C(═O)N[CH(CH₃)₂]₂ — 3060 CH₂ ClOCF₃ H H C(═O)(1-morpholinyl) — 3061 CH₂ Cl OCF₃ H H SO₂C₆H₅ — 3062 CH₂Cl OCF₃ H H SO₂(4-CH₃—C₆H₄) — 3063 CH₂ Cl OCF₃ H H SO₂(4-OCH₃—C₆H₄) —3064 CH₂ Cl OCF₃ H H SO₂-(2-thienyl) — 3065 CH₂ Cl OCF₃ H H SO₂CH₂C₆H₅ —3066 CH₂ Cl OCF₃ H H SO₂C₃H₇ — 3067 CH₂ Cl OCF₃ H H SO₂C₄H₉ — 3068 CH₂Cl OCF₃ H H C(═O)-(2-Cl—C₆H₄) — 3069 CH₂ Cl CH₃ H H C(═O)OC₂H₅ — 3070CH₂ Cl CH₃ H H C(═O)OC₃H₇ — 3071 CH₂ Cl CH₃ H H C(═O)OC₄H₉ — 3072 CH₂ ClCH₃ H H C(═O)OCH(CH₃)₂ — 3073 CH₂ Cl CH₃ H H C(═O)OCH₂CH(CH₃)₂ — 3074CH₂ Cl CH₃ H H C(═O)N(CH₃)₂ — 3075 CH₂ Cl CH₃ H H C(═O)N(C₂H₅)₂ — 3076CH₂ Cl CH₃ H H C(═O)N[CH(CH₃)₂]₂ — 3077 CH₂ Cl CH₃ H HC(═O)(1-morpholinyl) — 3078 CH₂ Cl CH₃ H H SO₂C₆H₅ — 3079 CH₂ Cl CH₃ H HSO₂(4-CH₃—C₆H₄) — 3080 CH₂ Cl CH₃ H H SO₂(4-OCH₃—C₆H₄) — 3081 CH₂ Cl CH₃H H SO₂-(2-thienyl) — 3082 CH₂ Cl CH₃ H H SO₂CH₂C₆H₅ — 3083 CH₂ Cl CH₃ HH SO₂C₃H₇ — 3084 CH₂ Cl CH₃ H H SO₂C₄H₉ — 3085 CH₂ Cl CH₃ H HC(═O)-(2-Cl—C₆H₄) — 3086 CH₂ CF₃ Cl H H C(═O)OC₂H₅ — 3087 CH₂ CF₃ Cl H HC(═O)OC₃H₇ — 3088 CH₂ CF₃ Cl H H C(═O)OC₄H₉ — 3089 CH₂ CF₃ Cl H HC(═O)OCH(CH₃)₂ — 3090 CH₂ CF₃ Cl H H C(═O)OCH₂CH(CH₃)₂ — 3091 CH₂ CF₃ ClH H C(═O)N(CH₃)₂ — 3092 CH₂ CF₃ Cl H H C(═O)N(C₂H₅)₂ — 3093 CH₂ CF₃ Cl HH C(═O)N[CH(CH₃)₂]₂ — 3094 CH₂ CF₃ Cl H H C(═O)(1-morpholinyl) — 3095CH₂ CF₃ Cl H H SO₂C₆H₅ — 3096 CH₂ CF₃ Cl H H SO₂(4-CH₃—C₆H₄) — 3097 CH₂CF₃ Cl H H SO₂(4-OCH₃—C₆H₄) — 3098 CH₂ CF₃ Cl H H SO₂-(2-thienyl) — 3099CH₂ CF₃ Cl H H SO₂CH₂C₆H₅ — 3100 CH₂ CF₃ Cl H H SO₂C₃H₇ — 3101 CH₂ CF₃Cl H H SO₂C₄H₉ — 3102 CH₂ CF₃ Cl H H C(═O)-(2-Cl—C₆H₄) — 3103 CH₂ CF₃OCH₃ H H C(═O)OC₂H₅ — 3104 CH₂ CF₃ OCH₃ H H C(═O)OC₃H₇ — 3105 CH₂ CF₃OCH₃ H H C(═O)OC₄H₉ — 3106 CH₂ CF₃ OCH₃ H H C(═O)OCH(CH₃)₂ — 3107 CH₂CF₃ OCH₃ H H C(═O)OCH₂CH(CH₃)₂ — 3108 CH₂ CF₃ OCH₃ H H C(═O)N(CH₃)₂ —3109 CH₂ CF₃ OCH₃ H H C(═O)N(C₂H₅)₂ — 3110 CH₂ CF₃ OCH₃ H HC(═O)N[CH(CH₃)₂]₂ — 3111 CH₂ CF₃ OCH₃ H H C(═O)(1-morpholinyl) — 3112CH₂ CF₃ OCH₃ H H SO₂C₆H₅ — 3113 CH₂ CF₃ OCH₃ H H SO₂(4-CH₃—C₆H₄) — 3114CH₂ CF₃ OCH₃ H H SO₂(4-OCH₃—C₆H₄) — 3115 CH₂ CF₃ OCH₃ H HSO₂-(2-thienyl) — 3116 CH₂ CF₃ OCH₃ H H SO₂CH₂C₆H₅ — 3117 CH₂ CF₃ OCH₃ HH SO₂C₃H₇ — 3118 CH₂ CF₃ OCH₃ H H SO₂C₄H₉ — 3119 CH₂ CF₃ OCH₃ H HC(═O)-(2-Cl—C₆H₄) — 3120 CH₂ CF₃ F H H C(═O)OC₂H₅ — 3121 CH₂ CF₃ F H HC(═O)OC₃H₇ — 3122 CH₂ CF₃ F H H C(═O)OC₄H₉ — 3123 CH₂ CF₃ F H HC(═O)OCH(CH₃)₂ — 3124 CH₂ CF₃ F H H C(═O)OCH₂CH(CH₃)₂ — 3125 CH₂ CF₃ F HH C(═O)N(CH₃)₂ — 3126 CH₂ CF₃ F H H C(═O)N(C₂H₅)₂ — 3127 CH₂ CF₃ F H HC(═O)N[CH(CH₃)₂]₂ — 3128 CH₂ CF₃ F H H C(═O)(1-morpholinyl) — 3129 CH₂CF₃ F H H SO₂C₆H₅ — 3130 CH₂ CF₃ F H H SO₂(4-CH₃—C₆H₄) — 3131 CH₂ CF₃ FH H SO₂(4-OCH₃—C₆H₄) — 3132 CH₂ CF₃ F H H SO₂-(2-thienyl) — 3133 CH₂ CF₃F H H SO₂CH₂C₆H₅ — 3134 CH₂ CF₃ F H H SO₂C₃H₇ — 3135 CH₂ CF₃ F H HSO₂C₄H₉ — 3136 CH₂ CF₃ F H H C(═O)-(2-Cl—C₆H₄) — 3137 CH₂ CH₃ OCH₃ CH₃ HC(═O)OC₂H₅ — 3138 CH₂ CH₃ OCH₃ CH₃ H C(═O)OC₃H₇ — 3139 CH₂ CH₃ OCH₃ CH₃H C(═O)OC₄H₉ — 3140 CH₂ CH₃ OCH₃ CH₃ H C(═O)OCH(CH₃)₂ — 3141 CH₂ CH₃OCH₃ CH₃ H C(═O)OCH₂CH(CH₃)₂ — 3142 CH₂ CH₃ OCH₃ CH₃ H C(═O)N(CH₃)₂ —3143 CH₂ CH₃ OCH₃ CH₃ H C(═O)N(C₂H₅)₂ — 3144 CH₂ CH₃ OCH₃ CH₃ HC(═O)N(CH(CH₃)₂]₂ — 3145 CH₂ CH₃ OCH₃ CH₃ H C(═O)(1-morpholinyl) — 3146CH₂ CH₃ OCH₃ CH₃ H SO₂C₆H₅ — 3147 CH₂ CH₃ OCH₃ CH₃ H SO₂(4-CH₃—C₆H₄) —3148 CH₂ CH₃ OCH₃ CH₃ H SO₂(4-OCH₃—C₆H₄) — 3149 CH₂ CH₃ OCH₃ CH₃ HSO₂-(2-thienyl) — 3150 CH₂ CH₃ OCH₃ CH₃ H SO₂CH₂C₆H₅ — 3151 CH₂ CH₃ OCH₃CH₃ H SO₂C₃H₇ — 3152 CH₂ CH₃ OCH₃ CH₃ H SO₂C₄H₉ — 3153 CH₂ CH₃ OCH₃ CH₃H C(═O)-(2-Cl—C₆H₄) — 3154 CH₂ CH₃ OCH₃ Cl H C(═O)OC₂H₅ — 3155 CH₂ CH₃OCH₃ Cl H C(═O)OC₃H₇ — 3156 CH₂ CH₃ OCH₃ Cl H C(═O)OC₄H₉ — 3157 CH₂ CH₃OCH₃ Cl H C(═O)OCH(CH₃)₂ — 3158 CH₂ CH₃ OCH₃ Cl H C(═O)OCH₂CH(CH₃)₂ —3159 CH₂ CH₃ OCH₃ Cl H C(═O)N(CH₃)₂ — 3160 CH₂ CH₃ OCH₃ Cl HC(═O)N(C₂H₅)₂ — 3161 CH₂ CH₃ OCH₃ Cl H C(═O)N[CH(CH₃)₂]₂ — 3162 CH₂ CH₃OCH₃ Cl H C(═O)(1-morpholinyl) — 3163 CH₂ CH₃ OCH₃ Cl H SO₂C₆H₅ — 3164CH₂ CH₃ OCH₃ Cl H SO₂(4-CH₃—C₆H₄) — 3165 CH₂ CH₃ OCH₃ Cl HSO₂(4-OCH₃—C₆H₄) — 3166 CH₂ CH₃ OCH₃ Cl H SO₂-(2-thienyl) — 3167 CH₂ CH₃OCH₃ Cl H SO₂CH₂C₆H₅ — 3168 CH₂ CH₃ OCH₃ Cl H SO₂C₃H₇ — 3169 CH₂ CH₃OCH₃ Cl H SO₂C₄H₉ — 3170 CH₂ CH₃ OCH₃ Cl H C(═O)-(2-Cl—C₆H₄) — 3171 CH₂CH₃ OCH₃ F H C(═O)OC₂H₅ — 3172 CH₂ CH₃ OCH₃ F H C(═O)OC₃H₇ — 3173 CH₂CH₃ OCH₃ F H C(═O)OC₄H₉ — 3174 CH₂ CH₃ OCH₃ F H C(═O)OCH(CH₃)₂ — 3175CH₂ CH₃ OCH₃ F H C(═O)OCH₂CH(CH₃)₂ — 3176 CH₂ CH₃ OCH₃ F H C(═O)N(CH₃)₂— 3177 CH₂ CH₃ OCH₃ F H C(═O)N(C₂H₅)₂ — 3178 CH₂ CH₃ OCH₃ F HC(═O)N[CH(CH₃)₂]₂ — 3179 CH₂ CH₃ OCH₃ F H C(═O)(1-morpholinyl) — 3180CH₂ CH₃ OCH₃ F H SO₂C₆H₅ — 3181 CH₂ CH₃ OCH₃ F H SO₂(4-CH₃—C₆H₄) — 3182CH₂ CH₃ OCH₃ F H SO₂(4-OCH₃—C₆H₄) — 3183 CH₂ CH₃ OCH₃ F HSO₂-(2-thienyl) — 3184 CH₂ CH₃ OCH₃ F H SO₂CH₂C₆H₅ — 3185 CH₂ CH₃ OCH₃ FH SO₂C₃H₇ — 3186 CH₂ CH₃ OCH₃ F H SO₂C₄H₉ — 3187 CH₂ CH₃ OCH₃ F HC(═O)-(2-Cl—C₆H₄) — 3188 CH₂ CH₃ CH₃ H CH₃ C(═O)OC₂H₅ — 3189 CH₂ CH₃ CH₃H CH₃ C(═O)OC₃H₇ — 3190 CH₂ CH₃ CH₃ H CH₃ C(═O)OC₄H₉ — 3191 CH₂ CH₃ CH₃H CH₃ C(═O)OCH(CH₃)₂ — 3192 CH₂ CH₃ CH₃ H CH₃ C(═O)OCH₂CH(CH₃)₂ — 3193CH₂ CH₃ CH₃ H CH₃ C(═O)N(CH₃)₂ — 3194 CH₂ CH₃ CH₃ H CH₃ C(═O)N(C₂H₅)₂ —3195 CH₂ CH₃ CH₃ H CH₃ C(═O)N[CH(CH₃)₂]₂ — 3196 CH₂ CH₃ CH₃ H CH₃C(═O)(1-morpholinyl) — 3197 CH₂ CH₃ CH₃ H CH₃ SO₂C₆H₅ — 3198 CH₂ CH₃ CH₃H CH₃ SO₂(4-CH₃—C₆H₄) — 3199 CH₂ CH₃ CH₃ H CH₃ SO₂(4-OCH₃—C₆H₄) — 3200CH₂ CH₃ CH₃ H CH₃ SO₂-(2-thienyl) — 3201 CH₂ CH₃ CH₃ H CH₃ SO₂CH₂C₆H₅ —3202 CH₂ CH₃ CH₃ H CH₃ SO₂C₃H₇ — 3203 CH₂ CH₃ CH₃ H CH₃ SO₂C₄H₉ — 3204CH₂ CH₃ CH₃ H CH₃ C(═O)-(2-Cl—C₆H₄) — 3205 CH₂ Cl Cl H CH₃ C(═O)OC₂H₅ —3206 CH₂ Cl Cl H CH₃ C(═O)OC₃H₇ — 3207 CH₂ Cl Cl H CH₃ C(═O)OC₄H₉ — 3208CH₂ Cl Cl H CH₃ C(═O)OCH(CH₃)₂ — 3209 CH₂ Cl Cl H CH₃ C(═O)OCH₂CH(CH₃)₂— 3210 CH₂ Cl Cl H CH₃ C(═O)N(CH₃)₂ — 3211 CH₂ Cl Cl H CH₃ C(═O)N(C₂H₅)₂— 3212 CH₂ Cl Cl H CH₃ C(═O)N[CH(CH₃)₂]₂ — 3213 CH₂ Cl Cl H CH₃C(═O)(1-morpholinyl) — 3214 CH₂ Cl Cl H CH₃ SO₂C₆H₅ — 3215 CH₂ Cl Cl HCH₃ SO₂(4-CH₃—C₆H₄) — 3216 CH₂ Cl Cl H CH₃ SO₂(4-OCH₃—C₆H₄) — 3217 CH₂Cl Cl H CH₃ SO₂-Cl-thienyl) — 3218 CH₂ Cl Cl H CH₃ SO₂CH₂C₆H₅ — 3219 CH₂Cl Cl H CH₃ SO₂C₃H₇ — 3220 CH₂ Cl Cl H CH₃ SO₂C₄H₉ — 3221 CH₂ Cl Cl HCH₃ C(═O)-(2-Cl—C₆H₄) — 3222 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OC₂H₅ — 3223 CH₂CH₃ OCH₃ OCH₃ H C(═O)OC₃H₇ — 3224 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OC₄H₉ — 3225CH₂ CH₃ OCH₃ OCH₃ H C(═O)OCH(CH₃)₂ — 3226 CH₂ CH₃ OCH₃ OCH₃ HC(═O)OCH₂CH(CH₃)₂ — 3227 CH₂ CH₃ OCH₃ OCH₃ H C(═O)N(CH₃)₂ — 3228 CH₂ CH₃OCH₃ OCH₃ H C(═O)N(C₂H₅)₂ — 3229 CH₂ CH₃ OCH₃ OCH₃ H C(═O)N[CH(CH₃)₂]₂ —3230 CH₂ CH₃ OCH₃ OCH₃ H C(═O)(1-morpholinyl) — 3231 CH₂ CH₃ OCH₃ OCH₃ HSO₂C₆H₅ - 3232 CH₂ CH₃ OCH₃ OCH₃ H SO₂(4-CH₃—C₆H₄) — 3233 CH₂ CH₃ OCH₃OCH₃ H SO₂(4-OCH₃—C₆H₄) — 3234 CH₂ CH₃ OCH₃ OCH₃ H SO₂-(2-thienyl) —3235 CH₂ CH₃ OCH₃ OCH₃ H SO₂CH₂C₆H₅ — 3236 CH₂ CH₃ OCH₃ OCH₃ H SO₂C₃H₇ —3237 CH₂ CH₃ OCH₃ OCH₃ H SO₂C₄H₉ — 3238 CH₂ CH₃ OCH₃ OCH₃ HC(═O)-(2-Cl—C₆H₄) — 3239 O Cl Cl H H SO₂C₃H₇ — 3240 O Cl CF₃ H H SO₂C₃H₇— 3241 O Cl OCH₃ H H SO₂C₃H₇ — 3242 O Cl OCF₃ H H SO₂C₃H₇ — 3243 O ClCH₃ H H SO₂C₃H₇ — 3244 O CF₃ Cl H H SO₂C₃H₇ — 3245 O CF₃ OCH₃ H HSO₂C₃H₇ — 3246 O CH₃ OCH₃ CH₃ H SO₂C₃H₇ — 3247 O CH₃ OCH₃ Cl H SO₂C₃H₇ —3248 O CH₃ OCH₃ F H SO₂C₃H₇ — 3249 O CH₃ CH₃ H CH₃ SO₂C₃H₇ — 3250 O ClCl H CH₃ SO₂C₃H₇ — 3251 CH₂ Cl Cl H H C(═O)-(3-Cl—C₆H₄) 115-118

The methods used in the preparation of the compounds of Structure A ofTable 1 may be used for the compounds of Structure A of Table 4. Forexample, replacing variously-substituted pyridine- and pyrimidineboronicacids for benzeneboronic acids in the palladium-catalyzed arylcross-coupling method (see Examples 35 or 831) will afford the desired6-pyridyl- or 6-pyrimidylpurine compounds.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 4, with minorprocedural modifications where necessary and use of reagents of theappropriate structure.

TABLE 4

(A) (B)

(C) Ex. m.p., No. X R⁴ Z R⁵ Y R⁶ R^(1a) R^(1b) ° C.^(a) 4001 CH₂ CH₃ CHN(CH₃)₂ N H c-C₃H₅ c-C₃H₅ — 4002 CH₂ CH₃ CH N(CH₃)₂ N H CH₃ c-C₃H₅ —4003 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ c-C₃H₅ — 4004 CH₂ CH₃ CH N(CH₃)₂ N HC₃H₇ c-C₃H₅ — 4005 CH₂ CH₃ CH N(CH₃)₂ N H C₄H₉ c-C₃H₅ — 4006 CH₂ CH₃ CHN(CH₃)₂ N H CH₃ C₃H₇ — 4007 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ C₃H₇ — 4008 CH₂CH₃ CH N(CH₃)₂ N H C₃H₇ C₃H₇ — 4009 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ C₄H₉ —4010 CH₂ CH₃ CH N(CH₃)₂ N H H 4-CH₃O—C₆H₄ — 4011 O CH₃ CH N(CH₃)₂ N Hc-C₃H₅ c-C₃H₅ — 4012 O CH₃ CH N(CH₃)₂ N H CH₃ c-C₃H₅ — 4013 O CH₃ CHN(CH₃)₂ N H C₂H₅ c-C₃H₅ — 4014 O CH₃ CH N(CH₃)₂ N H C₃H₇ c-C₃H₅ — 4015 OCH₃ CH N(CH₃)₂ N H C₄H₉ c-C₃H₅ — 4016 O CH₃ CH N(CH₃)₂ N H CH₃ C₃H₇ —4017 O CH₃ CH N(CH₃)₂ N H C₂H₅ C₃H₇ — 4018 O CH₃ CH N(CH₃)₂ N H C₃H₇C₃H₇ — 4019 O CH₃ CH N(CH₃)₂ N H C₂H₅ C₄H₉ — 4020 O CH₃ CH N(CH₃)₂ N H H4-CH₃O—C₆H₄ — 4021 CH₂ CH₃ CH CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4022 CH₂ CH₃ CHCH₃ N CH₃ CH₃ c-C₃H₅ — 4023 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4024 CH₂CH₃ CH CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4025 CH₂ CH₃ CH CH₃ N CH₃ C₄H₉ c-C₃H₅ —4026 CH₂ CH₃ CH CH₃ N CH₃ CH₃ C₃H₇ — 4027 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅ C₃H₇— 4028 CH₂ CH₃ CH CH₃ N CH₃ C₃H₇ C₃H₇ — 4029 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅C₄H₉ — 4030 CH₂ CH₃ CH CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4031 O CH₃ CH CH₃ N CH₃c-C₃H₅ c-C₃H₅ — 4032 O CH₃ CH CH₃ N CH₃ CH₃ c-C₃H₅ — 4033 O CH₃ CH CH₃ NCH₃ C₂H₅ c-C₃H₅ — 4034 O CH₂ CH CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4035 O CH₃ CHCH₃ N CH₃ C₄H₉ c-C₃H₅ — 4036 O CH₃ CH CH₃ N CH₃ CH₃ C₃H₇ — 4037 O CH₃ CHCH₃ N CH₃ C₂H₅ C₃H₇ — 4038 O CH₃ CH CH₃ N CH₃ C₃H₇ C₃H₇ — 4039 O CH₃ CHCH₃ N CH₃ C₂H₅ C₄H₉ — 4040 O CH₃ CH CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4041 CH₂CH₃ CH SCH₃ N H c-C₃H₅ c-C₃H₅ — 4042 CH₂ CH₃ CH SCH₃ N H CH₃ c-C₃H₅ —4043 CH₂ CH₃ CH SCH₃ N H C₂H₅ c-C₃H₅ — 4044 CH₂ CH₃ CH SCH₃ N H C₃H₇c-C₃H₅ — 4045 CH₂ CH₃ CH SCH₃ N H C₄H₉ c-C₃H₅ — 4046 CH₂ CH₃ CH SCH₃ N HCH₃ C₃H₇ — 4047 CH₂ CH₃ CH SCH₃ N H C₂H₅ C₃H₇ — 4048 CH₂ CH₃ CH SCH₃ N HC₃H₇ C₃H₇ — 4049 CH₂ CH₃ CH SCH₃ N H C₂H₅ C₄H₉ — 4050 CH₂ CH₃ CH SCH₃ NH H 4-CH₃O—C₆H₄ — 4051 O CH₃ CH SCH₃ N H c-C₃H₅ c-C₃H₅ — 4052 O CH₃ CHSCH₃ N H CH₃ c-C₃H₅ — 4053 O CH₃ CH SCH₃ N H C₂H₅ c-C₃H₅ — 4054 O CH₃ CHSCH₃ N H C₃H₇ c-C₃H₅ — 4055 O CH₃ CH SCH₃ N H C₄H₉ c-C₃H₅ — 4056 O CH₃CH SCH₃ N H CH₃ C₃H₇ — 4057 O CH₃ CH SCH₃ N H C₂H₅ C₃H₇ — 4058 O CH₃ CHSCH₃ N H C₃H₇ C₃H₇ — 4059 O CH₃ CH SCH₃ N H C₂H₅ C₄H₉ — 4060 O CH₃ CHSCH₃ N H H 4-CH₃O—C₆H₄ — 4061 CH₂ SCH₃ N CH₃ N SCH₃ c-C₃H₅ c-C₃H₅ — 4062CH₂ SCH₃ N CH₂ N SCH₃ CH₃ c-C₃H₅ — 4063 CH₂ SCH₃ N CH₃ N SCH₃ C₂H₅c-C₃H₅ — 4064 CH₂ SCH₃ N CH₃ N SCH₃ C₃H₇ c-C₃H₅ — 4065 CH₂ SCH₃ N CH₃ NSCH₃ C₄H₉ c-C₃H₅ — 4066 CH₂ SCH₃ N CH₃ N SCH₃ CH₃ C₃H₇ — 4067 CH₂ SCH₃ NCH₃ N SCH₃ C₂H₅ C₃H₇ — 4068 CH₂ SCH₃ N CH₃ N SCH₃ C₃H₇ C₃H₇ — 4069 CH₂SCH₃ N CH₃ N SCH₃ C₂H₅ C₄H₉ — 4070 CH₂ SCH₃ N CH₃ N SCH₃ H 4-CH₃O—C₆H₄ —4071 O SCH₃ N CH₃ N SCH₃ c-C₃H₅ c-C₃H₅ — 4072 O SCH₃ N CH₃ N SCH₃ CH₃c-C₃H₅ — 4073 O SCH₃ N CH₃ N SCH₃ C₂H₅ c-C₃H₅ — 4074 O SCH₃ N CH₃ N SCH₃C₃H₇ c-C₃H₅ — 4075 O SCH₃ N CH₃ N SCH₃ C₄H₉ c-C₃H₅ — 4076 O SCH₃ N CH₃ NSCH₃ CH₃ C₃H₇ — 4077 O SCH₃ N CH₃ N SCH₃ C₂H₅ C₃H₇ — 4078 O SCH₃ N CH₃ NSCH₃ C₃H₇ C₃H₇ — 4079 O SCH₃ N CH₃ N SCH₃ C₂H₅ C₄H₉ — 4080 O SCH₃ N CH₃N SCH₃ H 4-CH₃O—C₆H₄ — 4081 CH₂ CH₃ N CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4082 CH₂CH₃ N CH₃ N CH₃ CH₃ c-C₃H₅ — 4083 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4084CH₂ CH₃ N CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4085 CH₂ CH₃ N CH₃ N CH₃ C₄H₉ c-C₃H₅ —4086 CH₂ CH₃ N CH₃ N CH₃ CH₃ C₃H₇ — 4087 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ C₃H₇ —4088 CH₂ CH₃ N CH₃ N CH₃ C₃H₇ C₃H₇ — 4089 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ C₄H₉— 4090 CH₂ CH₃ N CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4091 O CH₃ N CH₃ N CH₃ c-C₃H₅c-C₃H₅ — 4092 O CH₃ N CH₃ N CH₃ CH₃ c-C₃H₅ — 4093 O CH₃ N CH₃ N CH₃ C₂H₅c-C₃H₅ — 4094 O CH₃ N CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4095 O CH₃ N CH₃ N CH₃C₄H₉ c-C₃H₅ — 4096 O CH₃ N CH₃ N CH₃ CH₃ C₃H₇ — 4097 O CH₃ N CH₃ N CH₃C₂H₅ C₃H₇ — 4098 O CH₃ N CH₃ N CH₃ C₃H₇ C₃H₇ — 4099 O CH₃ N CH₃ N CH₃C₂H₅ C₄H₉ — 4100 O CH₃ N CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4101 CH₂ CH₃ CH CH₃ NH c-C₃H₅ c-C₃H₅ — 4102 CH₂ CH₃ CH CH₃ N H CH₃ c-C₃H₅ — 4103 CH₂ CH₃ CHCH₃ N H C₂H₅ c-C₃H₅ — 4104 CH₂ CH₃ CH CH₃ N H C₃H₇ c-C₃H₅ — 4105 CH₂ CH₃CH CH₃ N H C₄H₉ c-C₃H₅ — 4106 CH₂ CH₃ CH CH₃ N H CH₃ C₃H₇ — 4107 CH₂ CH₃CH CH₃ N H C₂H₅ C₃H₇ — 4108 CH₂ CH₃ CH CH₃ N H C₃H₇ C₃H₇ — 4109 CH₂ CH₃CH CH₃ N H C₂H₅ C₄H₉ — 4110 CH₂ CH₃ CH CH₃ N H H 4-CH₃O—C₆H₄ — 4111 OCH₃ CH CH₃ N H c-C₃H₅ c-C₃H₅ — 4112 O CH₃ CH CH₃ N H CH₃ c-C₃H₅ — 4113 OCH₃ CH CH₃ N H C₂H₅ c-C₃H₅ — 4114 O CH₃ CH CH₃ N H C₃H₇ c-C₃H₅ — 4115 OCH₃ CH CH₃ N H C₄H₉ c-C₃H₅ — 4116 O CH₃ CH CH₃ N H CH₃ C₃H₇ — 4117 O CH₃CH CH₃ N H C₂H₅ C₃H₇ — 4118 O CH₃ CH CH₃ N H C₃H₇ C₃H₇ — 4119 O CH₃ CHCH₃ N H C₂H₅ C₄H₉ — 4120 O CH₃ CH CH₃ N H H 4-CH₃O—C₆H₄ — 4121 CH₂ CH₃ NN(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4122 CH₂ CH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ —4123 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4124 CH₂ CH₃ N N(CH₃)₂ CH HC₃H₇ c-C₃H₅ — 4125 CH₂ CH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4126 CH₂ CH₃ NN(CH₃)₂ CH H CH₃ C₃H₇ — 4127 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4128 CH₂CH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4129 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ —4130 CH₂ CH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄ — 4131 O CH₃ N N(CH₃)₂ CH Hc-C₃H₅ c-C₃H₅ — 4132 O CH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4133 O CH₃ NN(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4134 O CH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4135O CH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4136 O CH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ —4137 O CH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4138 O CH₃ N N(CH₃)₂ CH H C₃H₇C₃H₇ — 4139 O CH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4140 O CH₃ N N(CH₃)₂ CH H H4-CH₃O—C₆H₄ — 4141 CH₂ CH₃ N CH₃ CH H c-C₃H₅ c-C₃H₅ — 4142 CH₂ CH₃ N CH₃CH H CH₃ c-C₃H₅ — 4143 CH₂ CH₃ N CH₃ CH H C₂H₅ c-C₃H₅ — 4144 CH₂ CH₃ NCH₃ CH H C₃H₇ c-C₃H₅ — 4145 CH₂ CH₃ N CH₃ CH H C₄H₉ c-C₃H₅ — 4146 CH₂CH₃ N CH₃ CH H CH₃ C₃H₇ — 4147 CH₂ CH₃ N CH₃ CH H C₂H₅ C₃H₇ — 4148 CH₂CH₃ N CH₃ CH H C₃H₇ C₃H₇ — 4149 CH₂ CH₃ N CH₃ CH H C₂H₅ C₄H₉ — 4150 CH₂CH₃ N CH₃ CH H H 4-CH₃O—C₆H₄ — 4151 O CH₃ N CH₃ CH H c-C₃H₅ c-C₃H₅ —4152 O CH₃ N CH₃ CH H CH₃ c-C₃H₅ — 4153 O CH₃ N CH₃ CH H C₂H₅ c-C₃H₅ —4154 O CH₃ N CH₃ CH H C₃H₇ c-C₃H₅ — 4155 O CH₃ N CH₃ CH H C₄H₉ c-C₃H₅ —4156 O CH₃ N CH₃ CH H CH₃ C₃H₇ — 4157 O CH₃ N CH₃ CH H C₂H₅ C₃H₇ — 4158O CH₃ N CH₃ CH H C₃H₇ C₃H₇ — 4159 O CH₃ N CH₃ CH H C₂H₅ C₄H₉ — 4160 OCH₃ N CH₃ CH H H 4-CH₃O—C₆H₄ — 4161 CH₂ OCH₃ N OCH₃ CH H c-C₃H₅ c-C₃H₅120-121 4162 CH₂ OCH₃ N OCH₃ CH H CH₃ c-C₃H₅ — 4163 CH₂ OCH₃ N OCH₃ CH HC₂H₅ c-C₃H₅ — 4164 CH₂ OCH₃ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4165 CH₂ OCH₃ NOCH₃ CH H C₄H₉ c-C₃H₅ — 4166 CH₂ OCH₃ N OCH₃ CH H CH₃ C₃H₇ oil 4167 CH₂OCH₃ N OCH₃ CH H C₂H₅ C₃H₇ — 4168 CH₂ OCH₃ N OCH₃ CH H C₃H₇ C₃H₇ — 4169CH₂ OCH₃ N OCH₃ CH H C₂H₅ C₄H₉ — 4170 CH₂ OCH₃ N OCH₃ CH H H 4-CH₃O—C₆H₄— 4171 O OCH₃ N OCH₃ CH H c-C₃H₅ c-C₃H₅ oil 4172 O OCH₃ N OCH₃ CH H CH₃c-C₃H₅ — 4173 O OCH₃ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4174 O OCH₃ N OCH₃ CH HC₃H₇ c-C₃H₅ — 4175 O OCH₃ N OCH₃ CH H C₄H₉ c-C₃H₅ — 4176 O OCH₃ N OCH₃CH H CH₃ C₃H₇ — 4177 O OCH₃ N OCH₃ CH H C₂H₅ C₃H₇ — 4178 O OCH₃ N OCH₃CH H C₃H₇ C₃H₇ — 4179 O OCH₃ N OCH₃ CH H C₂H₅ C₄H₉ — 4180 O OCH₃ N OCH₃CH H H 4-CH₃O—C₆H₄ — 4181 CH₂ OCH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4182CH₂ OCH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4183 CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅c-C₃H₅ — 4184 CH₂ OCH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4185 CH₂ OCH₃ NN(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4186 CH₂ OCH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4187CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4188 CH₂ OCH₃ N N(CH₃)₂ CH H C₃H₇C₃H₇ — 4189 CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4190 CH₂ OCH₃ N N(CH₃)₂CH H H 4-CH₃O—C₆H₄ — 4191 O OCH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4192 OOCH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4193 O OCH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅— 4194 O OCH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4195 O OCH₃ N N(CH₃)₂ CH HC₄H₉ c-C₃H₅ — 4196 O OCH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4197 O OCH₃ NN(CH₃)₂ CH H C₂H₅ C₃H₇ — 4198 O OCH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4199 OOCH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4200 O OCH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄— 4201 CH₂ N(CH₃)₂ N OCH₃ CH H c-C₃H₅ c-C₃H₅ — 4202 CH₂ N(CH₃)₂ N OCH₃CH H CH₃ c-C₃H₅ — 4203 CH₂ N(CH₃)₂ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4204 CH₂N(CH₃)₂ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4205 CH₂ N(CH₃)₂ N OCH₃ CH H C₄H₉c-C₃H₅ — 4206 CH₂ N(CH₃)₂ N OCH₃ CH H CH₃ C₃H₇ — 4207 CH₂ N(CH₃)₂ N OCH₃CH H C₂H₅ C₃H₇ — 4208 CH₂ N(CH₃)₂ N OCH₃ CH H C₃H₇ C₃H₇ — 4209 CH₂N(CH₃)₂ N OCH₃ CH H C₂H₅ C₄H₉ — 4210 CH₂ N(CH₃)₂ N OCH₃ CH H H4-CH₃O—C₆H₄ — 4211 O N(CH₃)₂ N OCH₃ CH H c-C₃H₅ c-C₃H₅ — 4212 O N(CH₃)₂N OCH₃ CH H CH₃ c-C₃H₅ — 4213 O N(CH₃)₂ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4214 ON(CH₃)₂ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4215 O N(CH₃)₂ N OCH₃ CH H C₄H₉ c-C₃H₅— 4216 O N(CH₃)₂ N OCH₃ CH H CH₃ C₃H₇ — 4217 O N(CH₃)₂ N OCH₃ CH H C₂H₅C₃H₇ — 4218 O N(CH₃)₂ N OCH₃ CH H C₃H₇ C₃H₇ — 4219 O N(CH₃)₂ N OCH₃ CH HC₂H₅ C₄H₉ — 4220 O N(CH₃)₂ N OCH₃ CH H H 4-CH₃O—C₆H₄ — 4221 CH₂ OCH₃ NOCH₃ CH H C₂H₅ 2-furanyl — 4222 CH₂ OCH₃ N OCH₃ CH H C₃H₇ 2-furanyl —4223 CH₂ OCH₃ N OCH₃ CH H C₂H₅ ^(b) — 4224 CH₂ OCH₃ N OCH₃ CH H C₃H₇^(b) — 4225 CH₂ OCH₃ N OCH₃ CH H C₂H₅ ^(b) — 4226 CH₂ OCH₃ N OCH₃ CH Hc-C₃H₅ ^(b) — 4227 CH₂ OCH₃ N OCH₃ CH H CH₃ CH═CHCH₃ — 4228 CH₂ OCH₃ NOCH₃ CH H C₃H₇ CH═CH₂ — 4229 CH₂ OCH₃ N OCH₃ CH H CH₃ C₆H₅ — 4230 CH₂OCH₃ N OCH₃ CH H CH₃ c-C₄H₇ — Key: ^(a) Where the compound is indicatedas an “oil”, spectral data is provided below: Example 4166 elementalanalysis: calc. for C₁₉H₂₅N₅O₂ C 64.20, H 7.10, N 19.70; observed C64.13, H 6.67, N 19.30. Example 4171 elemental analysis: calc. forC₂₀H₂₃N₅O₃ C 62.98, H 6.09, N 18.36; observed C 62.80, H 6.10, N 18.19.^(b) C≡C—CH₃

The methods used in the preparation of the compounds of Table 1 may beemployed in the synthesis of those compounds of Structure A in Table 5and Table 5A. The methods employed to make the analogues bearing abenzofuran group are illustrated in the following examples.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 5 and Table5A, with minor procedural modifications where necessary and use ofreagents of the appropriate structure.

EXAMPLE 5001 Preparation of9-Dicyclopropylmethyl-8-ethyl-6-(6-methyl-2,3-dihydrobenzofuran-5-yl)purine

Part A. Sodium hydride dispersion in mineral oil (5.05 g, 50% w/w, 105mmol) was washed with hexane and dried under vacuum. DMF (100 mL) wasadded, the slurry was cooled to 0° C., and treated with a solution ofm-cresol (10 mL, 95.6 mmol) in DMF (20 mL). The resulting mixture wasallowed to stir for 1 h, then was treated with chloromethyl methyl ether(8.00 mL, 105 mmol) by syringe. The mixture was stirred overnight, thenpoured into ethyl acetate (200 mL). This was washed with water (3×200mL) and brine (100 mL), and the aqueous phases were back-extracted insequence with ethyl acetate. The extracts were combined, dried overmagnesium sulfate, filtered and evaporated. The oily product waspurified by elution through a plug of silica gel with 10:90 ethylacetate-hexane. Evaporation then afforded the pure product,3-(methoxymethoxy)toluene, as an oil (13.93 g, 91.5 mmol, 96%). TLCR_(F) 0.46 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.17(1H, t, J=7.7 Hz), 6.86-6.81 (3H, m), 5.17 (2H, s), 3.48 (3H, s), 2.33(3H, s). MS (H₂O-GC/MS): m/e 153 (60), 121 (100).

Part B. A solution of 3-(methoxymethoxy)toluene (5.00 g, 32.9 mmol) andTMEDA (5.30 mL, 35.1 mmol) in THF (50 mL) was cooled to 0° C., andtreated with a hexane solution of n-butyllithium (22.0 mL, 1.6 M,35.2mmol). After 4 hours, the solution was cooled to −78° C., andtreated dropwise with ethylene oxide (2.00 mL, 40 mmol, condensed from alecture bottle through a cold-finger into a graduated dropping funnel).The mixture was allowed to stir and warm to ambient temperatureovernight, then was poured into satd. aq. ammonium chloride solution(120 mL). This was extracted with ethyl acetate (2×120 mL), and theextracts were washed in sequence with brine, combined, dried overmagnesium sulfate, filtered and evaporated. The residual oil wasseparated by column chromatography (10:90 ethyl acetate-hexane) toafford the desired product,2-[2-(methoxymethoxy)-4-methylphenyl]ethanol, as a viscous liquid (2.25g, 11.5 mmol, 35%), along with 2.50 g recovered starting material. The¹H NMR spectrum showed regioselectivity in excess of 10:1. TLC R_(F)0.09 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.06 (1H,d, J=7.7 Hz), 6.92 (1H, br s), 6.78 (1H, br d, J=7.7 Hz), 5.20 (2H, s),3.83 (2H, q, J=6.4 Hz), 3.49 (3H, s), 2.89 (2H, t, J=6.6 Hz), 2.32 (3H,s), 1.61 (1H, t, J=5.9 Hz). MS (NH₃-DCI): m/e 214 (76), 212 (100), 197(9), 182 (30), 165 (38).

Part C. A solution of the MOM compound from Part B (1.84 g, 9.38 mmol)was dissolved in 1:1 THF-isopropanol (20 mL), and treated with HCl indioxane (2.5 mL, 4 N, 10.0 mmol). The reaction was stirred at ambienttemperature overnight. Aqueous workup gave sufficiently pure product,2-(2-hydroxy-4-methylphenyl)ethanol.

Part D. A solution of the diol from Part C (ca. 9 mmol) andtriphenylphosphine (2.83 g, 10.8 mmol) in THF (20 mL) was cooled to 0°C., and treated with diethyl azodicarboxylate (1.70 mL, 10.8 mmol) bysyringe. The solution was stirred overnight, then evaporated, and theresidue separated by a flash column to afford the product,6-methyl-2,3-dihydrobenzofuran (780 mg, 5.81 mmol, 65%). TLC R_(F) 0.29(2:98 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.07 (1H, d,J=7.4 Hz), 6.66 (1H, d, J=7.4 Hz), 6.62 (1H, s), 4.54 (2H, t, J=8.6 Hz),3.16 (2H, t, J=8.6 Hz), 2.30 (3H, s). MS (D₂O-GC/MS): m/e 135 (100).

Part E. A solution of the above compound (780 mg) and N-bromosuccinimide(1.24 g, 6.97 mmol) in dichloroethane (10 mL) was heated to refluxovernight, then cooled, filtered and evaporated. Column chromatography(hexane, then 2:98 ethyl acetate-hexane) gave first5-bromo-6-methylbenzofuran (270 mg, 1.27 mmol, 22%), then5-bromo-6-methyl-2,3-dihydrobenzofuran (923 mg, 4.33 mol, 75%), both assolids. For the dihydro product: TLC R_(F) 0.35 (2:98 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.31 (1H, s), 6.68 (1H, s),4.56 (2H, t, J=8.8 Hz), 3.17 (2H, t, J=8.8 Hz), 2.33 (3H, s). MS(H₂O-GC/MS): m/e 215 (76), 213 (100).

Part F. A solution of the bromide from Part E (923 mg, 4.33 mmol) intetrahydrofuran (20 mL) was cooled to −78° C., and treated with a hexanesolution of n-butyllithium (3.0 mL, 1.6 M, 4.8 mmol). After 1 hour, thereaction mixture was treated with triisopropylborate (1.00 mL, 4.33mmol) and allowed to come to ambient temperature over 6 hrs. Then, 1 mLof 6 N aq. HCl and 3 mL water were added, and the resulting mixture wasallowed to stir for 1 hr. It was poured into water (100 mL), andextracted with ethyl acetate (2×100 mL). The extracts were washed withbrine (60 mL), combined, dried over sodium sulfate, filtered andevaporated to afford a solid, which was purified by trituration withhexane to give 6-methyl-2,3-dihydrobenzofuran-5-boronic acid (718 mg,4.03 mmol, 93%).

Part G. A mixture of the boronic acid from Part F (298 mg, 1.67 mmol),6-chloro-9-dicyclopropylmethyl-8-ethylpurine (309 mg, 1.12 mmol), 2 Naqueous sodium carbonate solution (1.7 mL, 3.4 mmol) andtriphenylphosphine (61 mg, 0.233 mmol) in DME (20 mL) was degassed byrepeated cycles of brief vacuum pumping followed by nitrogen purging. Tothis was added palladium(II) acetate (13 mg, 0.058 mmol), and themixture was degassed again and then heated to reflux for 14 hours. Itwas cooled, and poured into water (100 mL). This mixture was extractedwith ethyl acetate (2×100 mL), and the extracts were washed in sequencewith brine (60 mL), combined, dried over sodium sulfate, filtered andevaporated. The residual material was separated by column chromatography(silica gel, 20:80 ethyl acetate-hexane) to afford the title product asa solid. This was recrystallized to purity from ether (253 mg, 0.77mmol, 69%). m.p. 147-148° C. TLC R_(F) 0.18 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.88 (1H, s), 7.60 (1H, s),6.77 (1H, s), 4.61 (2H, t, J=8.6 Hz), 3.44 (1H, v br), 3.24 (2H, t,J=8.6 Hz), 2.94 (2H, br), 2.44 (3H, s), 2.03 (2H, v br), 1.45 (3H, br t,J=6 Hz), 0.89-0.79 (2H, m), 0.58 (2H, br), 0.50-0.40 (2H, m), 0.27-0.17(2H, m). MS (NH₃-CI): m/e 377 (4), 376 (27), 375 (100). Analysis calc'dfor C₂₃H₂₆N₄O: C, 73.77; H, 7.01; N, 14.96; found: C, 73.69; H, 7.08; N,14.40.

EXAMPLES 5201, 5231 AND 5232 Preparation of9-Dicyclopropylmethyl-8-ethyl-6-(6-methylbenzofuran-5-yl)purine,6-(2-Bromo-6-methylbenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurineand6-(7-Bromo-6-methyl-2,3-dihydrobenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine

A solution of the compound of Example 5001 (250 mg, 0.668 mmol) andN-bromosuccinimide (119 mg, 0.669 mmol) in 1,2-dichloroethane (10 mL)was heated to reflux for 12 hours, then cooled and evaporated. Theresulting mixture was taken up in ether, filtered and evaporated, andthe residual material was separated by flash chromatography (silica gel,20:80 ethyl acetate-hexane) to afford, in order, the following threeproducts:6-(2-Bromo-6-methylbenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine:m.p. 177-178° C. TLC R_(F) 0.23 (20:80 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): d 8.92 (1H, s), 7.85 (1H, s), 7.42 (1H, s), 6.74 (1H,s), 4.15 (1H, v br), 2.97 (2H, v br), 2.54 (3H, s), 2.00 (2H, v br),1.44 (3H, br t, J=7 Hz), 0.90-0.80 (2H, m), 0.63-0.53 (2H, m), 0.50-0.40(2H, m), 0.26-0.16 (2H, m). MS (NH₃—CI): m/e calc'd for C₂₃H₂₄BrN₄O:451.1133, found 451.1132; 455 (3), 454 (25), 453 (99), 452 (31), 451(100).

9-Dicyclopropylmethyl-8-ethyl-6-(6-methylbenzofuran-5-yl)purine: m.p.139-141° C. TLC R_(F) 0.16 (20:80 ethyl acetate-hexane). ¹H NMR (300MHz, CDCl₃): d 8.92 (1H, s), 7.95 (1H, s), 7.60 (1H, d, J=2.2 Hz), 7.48(1H, d, J=0.7 Hz), 6.78 (1H, dd, J=2.2, 0.7 Hz), 4.40 (1H, v br), 2.97(2H, v br), 2.56 (3H, s), 2.04 (2H, v br), 1.44 (3H, br t, J=7 Hz),0.90-0.80 (2H, m), 0.62-0.52 (2H, m), 0.51-0.41 (2H, m), 0.29-0.18 (2H,m). MS (NH₃—CI): m/e calc'd for C₂₃H₂₅N₄O: 373.2028, found 373.2033; 375(3), 374 (26), 373 (100).

6-(7-Bromo-6-methyl-2,3-dihydrobenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine:m.p. 179-180° C. TLC R_(F) 0.04 (20:80 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): d 8.89 (1H, s), 7.47 (1H, s), 4.73 (2H, t, J=8.6 Hz),3.80 (1H, v br), 3.37 (2H, t, J=8.6 Hz), 2.95 (2H, v br), 2.44 (3H, s),1.44 (3H, br t, J=7 Hz), 0.89-0.79 (2H, m), 0.61-0.52 (2H, m), 0.51-0.41(2H, m), 0.28-0.18 (2H, m). MS (NH₃—CI): m/e calc'd for C₂₃H₂₆BrN₄O:453.1290, found 453.1285; 455 (98), 453 (100).

TABLE 5

(A) (B)

(C) Ex. m.p., No. X R³ R⁴ a b c R^(1a) R^(1b) ° C. 5001 CH₂ H CH₃ CH₂CH₂ O c-C₃H₅ c-C₃H₅ 147-148 5002 CH₂ H CH₃ CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ —5003 CH₂ H CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ — 5004 CH₂ H CH₃ CH₂ CH₂ O C₂H₅c-C₃H₅ — 5005 CH₂ H CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5006 CH₂ H CH₃ CH₂ CH₂ OC₄H₉ c-C₃H₅ — 5007 CH₂ H CH₃ CH₂ CH₂ O C₂H₅ C₃H₇ — 5008 CH₂ H CH₃ CH₂CH₂ O C₂H₅ C₄H₉ — 5009 CH₂ H CH₃ CH₂ CH₂ O C₃H₇ C₃H₇ — 5010 CH₂ H CH₃CH₂ CH₂ O CH₃ C₃H₇ — 5011 CH₂ H CH₃ O CH₂ O c-C₃H₅ c-C₃H₅ 168-169 5012CH₂ H CH₃ O CH₂ O H 4-(CH₃O)—C₆H₄ — 5013 CH₂ H CH₃ O CH₂ O CH₃ c-C₃H₅ —5014 CH₂ H CH₃ O CH₂ O C₂H₅ c-C₃H₅ — 5015 CH₂ H CH₃ O CH₂ O C₃H₇ c-C₃H₅— 5016 CH₂ H CH₃ O CH₂ O C₄H₉ c-C₃H₅ — 5017 CH₂ H CH₃ O CH₂ O C₂H₅ C₃H₇— 5018 CH₂ H CH₃ O CH₂ O C₂H₅ C₄H₉ — 5019 CH₂ H CH₃ O CH₂ O C₃H₇ C₃H₇ —5020 CH₂ H CH₃ O CH₂ O CH₃ C₃H₇ — 5021 CH₂ H CH₃ O CH₂ CH₂ c-C₃H₅ c-C₃H₅— 5022 CH₂ H CH₃ O CH₂ CH₂ H 4-(CH₃O)—C₆H₄ — 5023 CH₂ H CH₃ O CH₂ CH₂CH₃ c-C₃H₅ — 5024 CH₂ H CH₃ O CH₂ CH₂ C₂H₅ c-C₃H₅ — 5025 CH₂ H CH₃ O CH₂CH₂ C₃H₇ c-C₃H₅ — 5026 CH₂ H CH₃ O CH₂ CH₂ C₄H₉ c-C₃H₅ — 5027 CH₂ H CH₃O CH₂ CH₂ C₂H₅ C₃H₇ — 5028 CH₂ H CH₃ O CH₂ CH₂ C₂H₅ C₄H₉ — 5029 CH₂ HCH₃ O CH₂ CH₂ C₃H₇ C₃H₇ — 5030 CH₂ H CH₃ O CH₂ CH₂ CH₃ C₃H₇ — 5031 CH₂ HCH₃ CH₂ O CH₂ c-C₃H₅ c-C₃H₅ — 5032 CH₂ H CH₃ CH₂ O CH₂ H 4-(CH₃O)—C₆H₄ —5033 CH₂ H CH₃ CH₂ O CH₂ CH₃ c-C₃H₅ — 5034 CH₂ H CH₃ CH₂ O CH₂ C₂H₅c-C₃H₅ — 5035 CH₂ H CH₃ CH₂ O CH₂ C₃H₇ c-C₃H₅ — 5036 CH₂ H CH₃ CH₂ O CH₂C₄H₉ c-C₃H₅ — 5037 CH₂ H CH₃ CH₂ O CH₂ C₂H₅ C₃H₇ — 5038 CH₂ H CH₃ CH₂ OCH₂ C₂H₅ C₄H₉ — 5039 CH₂ H CH₃ CH₂ O CH₂ C₃H₇ C₃H₇ — 5040 CH₂ H CH₃ CH₂O CH₂ CH₃ C₃H₇ — 5041 CH₂ H Cl CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5042 CH₂ H ClCH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5043 CH₂ H Cl CH₂ CH₂ O CH₃ c-C₃H₅ — 5044CH₂ H Cl CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5045 CH₂ H Cl CH₂ CH₂ O C₃H₇ c-C₃H₅ —5046 CH₂ H Cl CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5047 CH₂ H Cl CH₂ CH₂ O C₂H₅ C₃H₇— 5048 CH₂ H Cl CH₂ CH₂ O C₂H₅ C₄H₉ — 5049 CH₂ H Cl CH₂ CH₂ O C₃H₇ C₃H₇5050 CH₂ H Cl CH₂ CH₂ O CH₃ C₃H₇ — 5051 CH₂ H Cl O CH₂ O c-C₃H₅ c-C₃H₅ —5052 CH₂ H Cl O CH₂ O H 4-(CH₃O)—C₆H₄ — 5053 CH₂ H Cl O CH₂ O CH₃ c-C₃H₅— 5054 CH₂ H Cl O CH₂ O C₂H₅ c-C₃H₅ — 5055 CH₂ H Cl O CH₂ O C₃H₇ c-C₃H₅— 5056 CH₂ H Cl O CH₂ O C₄H₉ c-C₃H₅ — 5057 CH₂ H Cl O CH₂ O C₂H₅ C₃H₇ —5058 CH₂ H Cl O CH₂ O C₂H₅ C₄H₉ — 5059 CH₂ H Cl O CH₂ O C₃H₇ C₃H₇ — 5060CH₂ H Cl O CH₂ O CH₃ C₃H₇ — 5061 O H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₂H₅ — 5062O H CH₃ CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5063 O H CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ —5064 O H CH₃ CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5065 O H CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅— 5066 O H CH₃ CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5067 O H CH₃ CH₂ CH₂ O C₂H₅ C₃H₇— 5068 O H CH₃ CH₂ CH₂ O C₂H₅ C₄H₉ — 5069 O H CH₃ CH₂ CH₂ O C₃H₇ C₃H₇ —5070 O H CH₃ CH₂ CH₂ O CH₃ C₃H₇ — 5071 O H CH₃ O CH₂ O c-C₃H₅ c-C₃H₅ —5072 O H CH₃ O CH₂ O H 4-(CH₃O)—C₆H₄ — 5073 O H CH₃ O CH₂ O CH₃ c-C₃H₅ —5074 O H CH₃ O CH₂ O C₂H₅ c-C₃H₅ — 5075 O H CH₃ O CH₃ O C₃H₇ c-C₃H₅ —5076 O H CH₃ O CH₂ O C₄H₉ c-C₃H₅ — 5077 O H CH₃ O CH₂ O C₂H₅ C₃H₇ — 5078O H CH₃ O CH₂ O C₂H₅ C₄H₉ — 5079 O H CH₃ O CH₂ O C₃H₇ C₃H₇ — 5080 O HCH₃ O CH₂ O CH₃ C₃H₇ — 5081 O H Cl CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5082 O H ClCH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5083 O H Cl CH₂ CH₂ O CH₃ c-C₃H₅ — 5084 O HCl CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5085 O H Cl CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5086 O HCl CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5087 O H Cl CH₂ CH₂ O C₂H₅ C₃H₇ — 5088 O H ClCH₂ CH₂ O C₂H₅ C₄H₉ — 5089 O H Cl CH₂ CH₂ O C₃H₇ C₃H₇ — 5090 O H Cl CH₂CH₂ O CH₃ C₃H₇ — 5091 O H Cl O CH₂ O c-C₃H₅ c-C₃H₅ — 5092 O H Cl O CH₂ OH 4-(CH₃O)—C₆H₄ — 5093 O H Cl O CH₂ O CH₃ c-C₃H₅ — 5094 O H Cl O CH₂ OC₂H₅ c-C₃H₅ — 5095 O H Cl O CH₂ O C₃H₇ c-C₃H₅ — 5096 O H Cl O CH₂ O C₄H₉c-C₃H₅ — 5097 O H Cl O CH₂ O C₂H₅ C₃H₇ — 5098 O H Cl O CH₂ O C₂H₅ C₄H₉ —5099 O H Cl O CH₂ O C₃H₇ C₃H₇ — 5100 O H Cl O CH₂ O CH₃ C₃H₇ — 5101 CH₂CH₃ CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5102 CH₂ CH₃ CH₃ CH₂ CH₂ O H4-(CH₃O)—C₆H₄ — 5103 CH₂ CH₃ CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ — 5104 CH₂ CH₃ CH₃CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5105 CH₂ CH₃ CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5106CH₂ CH₃ CH₃ CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5107 CH₂ CH₃ CH₃ CH₂ CH₂ O C₂H₅ C₃H₇— 5108 CH₂ CH₃ CH₃ CH₂ CH₂ O C₂H₅ C₄H₉ — 5109 CH₂ CH₃ CH₃ CH₂ CH₂ O C₃H₇C₃H₇ — 5110 CH₂ CH₃ CH₃ CH₂ CH₂ O CH₃ C₃H₇ — 5111 CH₂ H Cl O C═O NHc-C₃H₅ c-C₃H₅ — 5112 CH₂ H Cl O C═O NH H 4-(CH₃O)—C₆H₄ — 5113 CH₂ H Cl OC═O NH CH₃ c-C₃H₅ — 5114 CH₂ H Cl O C═O NH C₂H₅ c-C₃H₅ — 5115 CH₂ H Cl OC═O NH C₃H₇ c-C₃H₅ — 5116 CH₂ H Cl O C═O NH C₄H₉ c-C₃H₅ — 5117 CH₂ H ClO C═O NH C₂H₅ C₃H₇ — 5118 CH₂ H Cl O C═O NH C₂H₅ C₄H₉ — 5119 CH₂ H Cl CC═O NH C₃H₇ C₃H₇ — 5120 CH₂ H Cl O C═O NH CH₃ C₃H₇ — 5121 CH₂ H Cl O C═ONCH₃ c-C₃H₅ c-C₃H₅ — 5122 CH₂ H Cl O C═O NCH₃ H 4-(CH₃O)—C₆H₄ — 5123 CH₂H Cl O C═O NCH₃ CH₃ c-C₃H₅ — 5124 CH₂ H Cl O C═O NCH₃ C₂H₅ c-C₃H₅ — 5125CH₂ H Cl O C═O NCH₃ C₃H₇ c-C₃H₅ — 5126 CH₂ H Cl O C═O NCH₃ C₄H₉ c-C₃H₅ —5127 CH₂ H Cl O C═O NCH₃ C₂H₅ C₃H₇ — 5128 CH₂ H Cl O C═O NCH₃ C₂H₅ C₄H₉— 5129 CH₂ H Cl O C═O NCH₃ C₃H₇ C₃H₇ — 5130 CH₂ H Cl O C═O NCH₃ CH₃ C₃H₇— 5131 CH₂ H Cl O CCH₃ N c-C₃H₅ c-C₃H₅ — 5132 CH₂ H Cl O CCH₃ N H4-(CH₃O)-C₆H₄ — 5133 CH₂ H Cl O CCH₃ N CH₃ c-C₃H₅ — 5134 CH₂ H Cl O CCH₃N C₂H₅ c-C₃H₅ — 5135 CH₂ H Cl O CCH₃ N C₃H₇ c-C₃H₅ — 5136 CH₂ H Cl OCCH₃ N C₄H₉ c-C₃H₅ — 5137 CH₂ H Cl O CCH₃ N C₂H₅ C₃H₇ — 5138 CH₂ H Cl OCCH₃ N C₂H₅ C₄H₉ — 5139 CH₂ H Cl O CCH₃ N C₃H₇ C₃H₇ — 5140 CH₂ H Cl OCCH₃ N CH₃ C₃H₇ — 5141 CH₂ H Cl O C═O NC₂H₅ c-C₃H₅ c-C₃H₅ — 5142 CH₂ HCl O C═O NC₂H₅ H 4-(CH₃O)—C₆H₄ — 5143 CH₂ H Cl O C═O NC₂H₅ CH₃ c-C₃H₅ —5144 CH₂ H Cl O C═O NC₂H₅ C₂H₅ c-C₃H₅ — 5145 CH₂ H Cl O C═O NC₂H₅ C₃H₇c-C₃H₅ — 5146 CH₂ H Cl O C═O NC₂H₅ C₄H₉ c-C₃H₅ — 5147 CH₂ H Cl O C═ONC₂H₅ C₂H₅ C₃H₇ — 5148 CH₂ H Cl O C═O NC₂H₅ C₂H₅ C₄H₉ — 5149 CH₂ H Cl OC═O NC₂H₅ C₃H₇ C₃H₇ — 5150 CH₂ H Cl O C═O NC₂H₅ CH₃ C₃H₇ — 5151 CH₂ H ClO C═O O c-C₃H₅ c-C₃H₅ — 5152 CH₂ H Cl O C═O O H 4-(CH₃O)—C₆H₄ — 5153 CH₂H Cl O C═O O CH₃ c-C₃H₅ — 5154 CH₂ H Cl O C═O O C₂H₅ c-C₃H₅ — 5155 CH₂ HCl O C═O O C₃H₇ c-C₃H₅ — 5156 CH₂ H Cl O C═O O C₄H₉ c-C₃H₅ — 5157 CH₂ HCl O C═O C C₂H₅ C₃H₇ — 5158 CH₂ H Cl O C═O O C₂H₅ C₄H₉ — 5159 CH₂ H Cl OC═O O C₃H₇ C₃H₇ — 5160 CH₂ H Cl O C═O O CH₃ C₃H₇ — 5161 CH₂ H Cl OCH₂CH₂ O c-C₃H₅ c-C₃H₅ — 5162 CH₂ H Cl O CH₂CH₂ O H 4-(CH₃O)—C₆H₄ — 5163CH₂ H Cl O CH₂CH₂ O CH₃ c-C₃H₅ — 5164 CH₂ H Cl O CH₂CH₂ O C₂H₅ c-C₃H₅ —5165 CH₂ H Cl O CH₂CH₂ O C₃H₇ c-C₃H₅ — 5166 CH₂ H Cl O CH₂CH₂ O C₄H₉c-C₃H₅ — 5167 CH₂ H Cl O CH₂CH₂ O C₂H₅ C₃H₇ — 5168 CH₂ H Cl O CH₂CH₂ OC₂H₅ C₄H₉ — 5169 CH₂ H Cl O CH₂CH₂ O C₃H₇ C₃H₇ — 5170 CH₂ H Cl O CH₂CH₂O CH₃ C₃H₇ — 5171 CH₂ H CH₃ O C═O O c-C₃H₅ c-C₃H₅ — 5172 CH₂ H CH₃ O C═OO H 4-(CH₃O)—C₆H₄ — 5173 CH₂ H CH₃ O C═O O CH₃ c-C₃H₅ — 5174 CH₂ H CH₃ OC═O O C₂H₅ c-C₃H₅ — 5175 CH₂ H CH₃ O C═O O C₃H₇ c-C₃H₅ — 5176 CH₂ H CH₃O C═O O C₄H₉ c-C₃H₅ — 5177 CH₂ H CH₃ O C═O O C₂H₅ C₃H₇ — 5178 CH₂ H CH₃O C═O O C₂H₅ C₄H₉ — 5179 CH₂ H CH₃ O C═O O C₃H₇ C₃H₇ — 5180 CH₂ H CH₃ OC═O O CH₃ C₃H₇ — 5181 CH₂ H CH₃ O CH₂CH₂ O c-C₃H₅ c-C₃H₅ — 5182 CH₂ HCH₃ O CH₂CH₂ O H 4-(CH₃O)—C₆H₄ — 5183 CH₂ H CH₃ O CH₂CH₂ O CH₃ c-C₃H₅ —5184 CH₂ H CH₃ O CH₂CH₂ O C₂H₅ c-C₃H₅ — 5185 CH₂ H CH₃ O CH₂CH₂ O C₃H₇c-C₃H₅ — 5186 CH₂ H CH₃ O CH₂CH₂ O C₄H₉ c-C₃H₅ — 5187 CH₂ H CH₃ O CH₂CH₂O C₂H₅ C₃H₇ — 5188 CH₂ H CH₃ O CH₂CH₂ O C₂H₅ C₄H₉ — 5189 CH₂ H CH₃ OCH₂CH₂ O C₃H₇ C₃H₇ — 5190 CH₂ H CH₃ O CH₂CH₂ O CH₃ C₃H₇ — 5191 CH₂ H ClO CH₂CH₂ NCH₃ c-C₃H₅ c-C₃H₅ — 5192 CH₂ H Cl O CH₂CH₂ NCH₃ H4-(CH₃O)—C₆H₄ — 5193 CH₂ H Cl O CH₂CH₂ NCH₃ CH₃ c-C₃H₅ — 5194 CH₂ H Cl OCH₂CH₂ NCH₃ C₂H₅ c-C₃H₅ — 5195 CH₂ H Cl O CH₂CH₂ NCH₃ C₃H₇ c-C₃H₅ — 5196CH₂ H Cl O CH₂CH₂ NCH₃ C₄H₉ c-C₃H₅ — 5197 CH₂ H Cl O CH₂CH₂ NCH₃ C₂H₅C₃H₇ — 5198 CH₂ H Cl O CH₂CH₂ NCH₃ C₂H₅ C₄H₉ — 5199 CH₂ H Cl O CH₂CH₂NCH₃ C₃H₇ C₃H₇ — 5200 CH₂ H Cl O CH₂CH₂ NCH₃ CH₃ C₃H₇ — 5201 CH₂ H CH₃CH CH O c-C₃H₅ c-C₃H₅ 139-141 5202 CH₂ H CH₃ CH CH O H 4-(CH₃O)—C₆H₄ —5203 CH₂ H CH₃ CH CH O CH₃ c-C₃H₅ — 5204 CH₂ H CH₃ CH CH O C₂H₅ c-C₃H₅ —5205 CH₂ H CH₃ CH CH O C₃H₇ c-C₃H₅ — 5206 CH₂ H CH₃ CH CH O C₄H₉ c-C₃H₅— 5207 CH₂ H CH₃ CH CH O C₂H₅ C₃H₇ — 5208 CH₂ H CH₃ CH CH O C₂H₅ C₄H₉ —5209 CH₂ H CH₃ CH CH O C₃H₇ C₃H₇ — 5210 CH₂ H CH₃ CH CH O CH₃ C₃H₇ —5211 CH₂ H Cl CH CH O c-C₃H₅ c-C₃H₅ — 5212 CH₂ H Cl CH CH O H4-(CH₃O)—C₆H₄ — 5213 CH₂ H Cl CH CH O CH₃ c-C₃H₅ — 5214 CH₂ H Cl CH CH OC₂H₅ c-C₃H₅ — 5215 CH₂ H Cl CH CH O C₃H₇ c-C₃H₅ — 5216 CH₂ H Cl CH CH OC₄H₉ c-C₃H₅ — 5217 CH₂ H Cl CH CH O C₂H₅ C₃H₇ — 5218 CH₂ H Cl CH CH OC₂H₅ C₄H₉ — 5219 CH₂ H Cl CH CH O C₃H₇ C₃H₇ — 5220 CH₂ H Cl CH CH O CH₃C₃H₇ — 5221 CH₂ H CH₃ CH CHCH CH c-C₃H₅ c-C₃H₅ — 5222 CH₂ H CH₃ CH CHCHCH H 4-(CH₃O)—C₆H₄ — 5223 CH₂ H CH₃ CH CHCH CH CH₃ c-C₃H₅ — 5224 CH₂ HCH₃ CH CHCH CH C₂H₅ c-C₃H₅ — 5225 CH₂ H CH₃ CH CHCH CH C₃H₇ c-C₃H₅ —5226 CH₂ H CH₃ CH CHCH CH C₄H₉ c-C₃H₅ — 5227 CH₂ H CH₃ CH CHCH CH C₂H₅C₃H₇ — 5228 CH₂ H CH₃ CH CHCH CH C₂H₅ C₄H₉ — 5229 CH₂ H CH₃ CH CHCH CHC₃H₇ C₃H₇ — 5230 CH₂ H CH₃ CH CHCH CH CH₃ C₃H₇ — 5231 CH₂ H CH₃ CH CBr Oc-C₃H₅ c-C₃H₅ 177-178 5232 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ 179-1805233 CH₂ H CH₃ CH CCH₃ O c-C₃H₅ c-C₃H₅ — 5234 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅c-C₃H₅ — 5235 CH₂ H CH₃ CH CSCH₃ O c-C₃H₅ c-C₃H₅ — 5236 CH₂ H CH₃ CH₂CH₂ O c-C₃H₅ c-C₃H₅ —

TABLE 5A

(A)

(B)

(C) Ex. m.p., No. X R¹² a b c R^(1a) R^(1b) ° C. 5232 CH₂ Br CH₂ CH₂ Oc-C₃H₅ c-C₃H₅ 179-180 5234 CH₂ CN CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5236 CH₂SCH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ —

The methods used in the preparation of the compounds of Table 1 may beused for the compounds of Structure A of Table 6. For example, replacingvariously-substituted penta atomic heteroaryl boronic acids forbenzeneboronic acids in the palladium-catalyzed aryl cross-couplingmethod (see Examples 35 or 831) will afford the desired6-heteroarylpurine compounds.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 6, with minorprocedural modifications where necessary and use of reagents of theappropriate structure.

TABLE 6

(A) (B)

(C) m.p. Ex. No. X R³ a b c d R^(1a) R^(1b) ° C.^(a) 6001 CH₂ H CCH₃ N OCCH₃ c-C₃H₅ c-C₃H₅ oil 6002 CH₂ H CCH₃ N O CCH₃ CH₃ c-C₃H₅ — 6003 CH₂ HCCH₃ N O CCH₃ C₂H₅ c-C₃H₅ — 6004 CH₂ H CCH₃ N O CCH₃ C₃H₇ c-C₃H₅ — 6005CH₂ H CCH₃ N O CCH₃ C₄H₉ c-C₃H₅ — 6006 CH₂ H CCH₃ N O CCH₃ CH₃ C₃H₇ —6007 CH₂ H CCH₃ N O CCH₃ C₂H₅ C₃H₇ — 6008 CH₂ H CCH₃ N O CCH₃ C₃H₇ C₃H₇— 6009 CH₂ H CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6010 CH₂ H CCH₃ N O CCH₃ H4-CH₃O—C₆H₄ — 6011 O H CCH₃ N O CCH₃ c-C₃H₅ c-C₃H₅ — 6012 O H CCH₃ N OCCH₃ CH₃ c-C₃H₅ — 6013 O H CCH₃ N O CCH₃ C₂H₅ c-C₃H₅ — 6014 O H CCH₃ N OCCH₃ C₃H₇ c-C₃H₅ — 6015 O H CCH₃ N O CCH₃ C₄H₉ c-C₃H₅ — 6016 O H CCH₃ NO CCH₃ CH₃ C₃H₇ — 6017 O H CCH₃ N O CCH₃ C₂H₅ C₃H₇ — 6018 O H CCH₃ N OCCH₃ C₃H₇ C₃H₇ — 6019 O H CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6020 O H CCH₃ N OCCH₃ H 4-CH₃O—C₆H₄ — 6021 CH₂ CH₃ CCH₃ N O CCH₃ c-C₃H₅ c-C₃H₅ — 6022 CH₂CH₃ CCH₃ N O CCH₃ CH₃ c-C₃H₅ — 6023 CH₂ CH₃ CCH₃ N O CCH₃ C₂H₅ c-C₃H₅ —6024 CH₂ CH₃ CCH₃ N O CCH₃ C₃H₇ c-C₃H₅ — 6025 CH₂ CH₃ CCH₃ N O CCH₃ C₄H₉c-C₃H₅ — 6026 CH₂ CH₃ CCH₃ N O CCH₃ CH₃ C₃H₇ — 6027 CH₂ CH₃ CCH₃ N OCCH₃ C₂H₅ C₃H₇ — 6028 CH₂ CH₃ CCH₃ N O CCH₃ C₃H₇ C₃H₇ — 6029 CH₂ CH₃CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6030 CH₂ CH₃ CCH₃ N O CCH₃ H 4-CH₃O—C₆H₄ —6031 CH₂ H CCH₃ N NCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6032 CH₂ H CCH₃ N NCH₃ CCH₃CH₃ c-C₃H₅ — 6033 CH₂ H CCH₃ N NCH₃ CCH₃ C₂H₅ c-C₃H₅ — 6034 CH₂ H CCH₃ NNCH₃ CCH₃ C₃H₇ c-C₃H₅ — 6035 CH₂ H CCH₃ N NCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6036CH₂ H CCH₃ N NCH₃ CCH₃ CH₃ C₃H₇ — 6037 CH₂ H CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇— 6038 CH₂ H CCH₃ N NCH₃ CCH₃ C₃H₇ C₃H₇ — 6039 CH₂ H CCH₃ N NCH₃ CCH₃C₂H₅ C₄H₉ — 6040 CH₂ H CCH₃ N NCH₃ CCH₃ H 4-CH₃O—C₆H₄ — 6041 O H CCH₃ NNCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6042 O H CCH₃ N NCH₃ CCH₃ CH₃ c-C₃H₅ — 6043 OH CCH₃ N NCH₃ CCH₃ C₂H₅ c-C₃H₅ — 6044 O H CCH₃ N NCH₃ CCH₃ C₃H₇ c-C₃H₅ —6045 O H CCH₃ N NCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6046 O H CCH₃ N NCH₂ CCH₃ CH₃C₃H₇ — 6047 O H CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇ — 6048 O H CCH₃ N NCH₃ CCH₃C₃H₇ C₃H₇ — 6049 O H CCH₃ N NCH₃ CCH₃ C₂H₅ C₄H₉ — 6050 O H CCH₃ N NCH₃CCH₃ H 4-CH₃O—C₆H₄ — 6051 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6052CH₂ CH₃ CCH₃ N NCH₃ CCH₃ CH₃ c-C₃H₅ — 6053 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅c-C₃H₅ — 6054 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₃H₇ c-C₃H₅ — 6055 CH₂ CH₃ CCH₃ NNCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6056 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ CH₃ C₃H₇ — 6057CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇ — 6058 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₃H₇C₃H₇ — 6059 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅ C₄H₉ — 6060 CH₂ CH₃ CCH₃ NNCH₃ CCH₃ H 4-CH₃O—C₆H₄ — 6061 CH₂ H CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ —6062 CH₂ H CCH₃ N NC₂H₅ CCH₃ CH₃ c-C₃H₅ — 6063 CH₂ H CCH₃ N NC₂H₅ CCH₃C₂H₅ c-C₃H₅ — 6064 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6065 CH₂ H CCH₃N NC₂H₅ CCH₃ C₄H₉ c-C₃H₅ — 6066 CH₂ H CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6067CH₂ H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₃H₇ — 6068 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₃H₇C₃H₇ — 6069 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6070 CH₂ H CCH₃ N NC₂H₅CCH₃ H 4-CH₃O—C₆H₄ — 6071 O H CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6072 O HCCH₃ N NC₂H₅ CCH₃ CH₃ c-C₃H₅ — 6073 O H CCH₃ N NC₂H₅ CCH₃ C₂H₅ c-C₃H₅ —6074 O H CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6075 O H CCH₃ N NC₂H₅ CCH₃ C₄H₉c-C₃H₅ — 6076 O H CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6077 O H CCH₃ N NC₂H₅CCH₃ C₂H₅ C₃H₇ — 6078 O H CCH₃ N NC₂H₅ CCH₃ C₃H₇ C₃H₇ — 6079 O H CCH₃ NNC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6080 O H CCH₃ N NC₂H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6081CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6082 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃CH₃ c-C₃H₅ — 6083 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₂H₅ c-C₃H₅ — 6084 CH₂ CH₃CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6085 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₄H₉c-C₃H₅ — 6086 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6087 CH₂ CH₃ CCH₃ NNC₂H₅ CCH₃ C₂H₅ C₃H₇ — 6088 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₃H₇ C₃H₇ — 6089CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6090 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ H4-CH₃O—C₆H₄ — 6091 CH₂ H CCH₃ N CCH₃ NCH₃ c-C₃H₅ c-C₃H₅ — 6092 CH₂ HCCH₃ N CCH₃ NCH₃ CH₃ c-C₃H₅ — 6093 CH₂ H CCH₃ N CCH₃ NCH₃ C₂H₅ c-C₃H₅ —6094 CH₂ H CCH₃ N CCH₃ NCH₃ C₃H₇ c-C₃H₅ — 6095 CH₂ H CCH₃ N CCH₃ NCH₃C₄H₉ c-C₃H₅ — 6096 CH₂ H CCH₃ N CCH₃ NCH₃ CH₃ C₃H₇ — 6097 CH₂ H CCH₃ NCCH₃ NCH₃ C₂H₅ C₃H₇ — 6098 CH₃ H CCH₃ N CCH₃ NCH₃ C₃H₇ C₃H₇ — 6099 CH₂ HCCH₃ N CCH₃ NCH₃ C₂H₅ C₄H₉ — 6100 CH₂ H CCH₃ N CCH₃ NCH₃ H 4-CH₃O—C₆H₄ —6101 CH₂ H CCH₃ N NC₆H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6102 CH₂ H CCH₃ N NC₆H₅CCH₃ CH₃ c-C₃H₅ — 6103 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6104 CH₂ HCCH₃ N NC₆H₅ CCH₃ C₃H₇ c-C₃H₅ — 6105 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅— 6106 CH₂ H CCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6107 CH₂ H CCH₃ N NC₆H₅ CCH₃C₂H₅ C₃H₇ — 6108 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6109 CH₂ H CCH₃ NNC₆H₅ CCH₃ C₂H₅ C₄H₉ — 6110 CH₂ H CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6111O H CCH₃ N NC₆H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6112 O H CCH₃ N NC₆H₅ CCH₃ CH₃c-C₃H₅ — 6113 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6114 O H CCH₃ N NC₆H₅CCH₃ C₃H₇ c-C₃H₅ — 6115 O H CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅ — 6116 O HCCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6117 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₃H₇ — 6118O H CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6119 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₄H₉ —6120 O H CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6121 CH₂ CH₃ CCH₃ N NC₆H₅CCH₃ c-C₃H₅ c-C₃H₅ — 6122 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ CH₃ c-C₃H₅ — 6123CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6124 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃C₃H₇ c-C₃H₅ — 6125 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅ — 6126 CH₂ CH₃CCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6127 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₃H₇ —6128 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6129 CH₂ CH₃ CCH₃ N NC₆H₅CCH₃ C₂H₅ C₄H₉ — 6130 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ — Key: a)Where the compound is indicated as an “oil”, spectral data is providedas follows: Example 6001 spectral data: MS (NH₃—CI): m/e 338 (M+H⁺,100%).

The methods used in the preparation of the compounds of Table 1 may beused for preparation of many of the compounds of Structure A of Table 7.The preparation of those compounds derived from cyclo addition ofcompounds with alkynyl-bearing R¹ groups is illustrated by the followingexamples.

The methods of Schemes 13 and 14 may be used to prepare many of theexamples of Structure B and Structure C contained in Table 7, with minorprocedural modifications where necessary and use of reagents of theappropriate structure.

EXAMPLE 7409 Preparation of9-[1-Cyclopropyl-1-(3-methyl-isoxazol-5-yl)methyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine

To a stirring solution of the compound of Example 7241 (90 mg, 0.24mmol; prepared in a manner similar to that of Example 2 using6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were addedchloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27mmol). (The chloroacetaldoxime used was previously prepared by reactingequimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, thenextracting the product into diethyl ether and washing with water.) Thecyclo addition reaction was monitored by TLC and additional amounts ofchloroacetaldoxime and triethylamine were added until all the startingmaterial was consumed. The reaction mixture was purified by addingdirectly to a column packed with silica gel and eluting using a gradientof 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam wascollected. MS (NH₃—CI) 428 (M+H⁺) HRMS: m/e=428.1037 (M+H⁺,C₂₁H₂₀Cl₂N₅O). Purity by reverse phase HPLC >97%.

EXAMPLES 7396 AND 7398 Preparation of6-(2,4-Dichlorophenyl)-9-[1-(3-ethoxycarbonyl-isoxazol-5-yl)butyl]-8-ethyl-9H-purineand9-[1-(4-Cyano-3-ethoxycarbonyl-isoxazol-5-yl)butyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine

A solution of the compound of Example 7259 (120 mg, 0.321 mmol; preparedin a manner similar to that of Example 2 using6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 1-hexyn-3-ol), ethylchlorooximidoacetate (146 mg, 0.963 mmol) and diisopropylethylamine (170μL, 0.976 mmol) in toluene (2 mL) was heated to reflux for 20 hours,then cooled and diluted with 20 mL ethyl acetate. This was washed withwater (2×20 mL) and satd. aq. brine (20 mL), and the aqueous phases wereback-extracted in sequence with ethyl acetate (20 mL). The organicextracts were combined, dried over anhydrous sodium sulfate, filteredand evaporated. The residual material was separated by columnchromatography (silica gel, 1:4 ethyl acetate-hexane) to afford, inorder, unreacted starting material (about 50 mg), then the compound ofExample 7396 (58.7 mg, 0.120 mmol, 37%), and finally the compound ofExample 7398 (23.8 mg, 0.046 mmol, 14%), the latter two compounds beingamorphous solids. Example 7396 spectral data: TLC R_(F) 0.27 (20:80ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): 6 8.96 (1H, s), 7.67(1H, d, J=8.1 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.1, 1.8 Hz),6.86 (1H, s), 5.83 (1H, dd, J=9.9, 6.2 Hz), 4.43 (2H, q, J=7.3 Hz), 2.98(2H, q, J=7.7 Hz), 2.91-2.78 (1H, m), 2.63-2.49 (1H, m), 1.42 (3H, t,J=7.7 Hz), 1.40 (3H, t, J=7.3 Hz), 1.39-1.19 (2H, m), 1.00 (3H, t, J=7.3Hz). MS (NH₃—CI): m/e calc'd for C₂₃H₂₄Cl₂N₅O₃: 488.1256, found488.1252; 493 (3), 492 (13), 491 (18), 490 (68), 489 (28), 488 (100).Example 7398 spectral data: TLC R_(F) 0.11 (20:80 ethyl acetate-hexane).¹H NMR (300 MHz, CDCl₃): 8 8.99 (1H, S), 7.72 (1H, d, J=8.1 Hz), 7.59(1H, J=1.8 Hz), 7.42 (1H, dd, J=8.1, 1.8 Hz), 5.40 (1H, dd, J=10.4, 5.0Hz), 4.42 (2H, q, J=7.4 Hz), 3.00-2.90 (2H, m), 2.66-2.52 (1H, m),2.51-2.38 (1H, m), 1.46 (3H, t, J=7.4 Hz), 1.41 (3H, t, J=7.3 Hz),1.40-1.10 (2H, m), 0.98 (3H, t, J=7.2 Hz). MS (NH₃—CI): m/e calc'd forC₂₄H₂₅Cl₂N₆O₄: 531.1315, found 531.1315; 531 (100).

TABLE 7

(A) (B)

(C) Ex. No. X R⁴ R⁵ R¹¹ R⁶ R^(1a) L G^(a) m.p., ° C.^(b) 7001 CH₂ CH₃CH₃ H CH₃ CH₃ bond G1 — 7002 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G1 — 7003 CH₂CH₃ CH₃ H CH₃ C₃H₇ bond G1 — 7004 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G1 —7005 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G2 — 7006 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G2— 7007 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G2 — 7008 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅bond G2 — 7009 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G3 — 7010 CH₂ CH₃ CH₃ H CH₃C₂H₅ bond G3 — 7011 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G3 — 7012 CH₂ CH₃ CH₃ HCH₃ c-C₃H₅ bond G3 — 7013 CH₂ CH₃ CH₃ H CH₃ CH₃ CH₂ G4 — 7014 CH₂ CH₃CH₃ H CH₃ C₂H₅ CH₂ G4 — 7015 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G4 — 7016 CH₂CH₃ CH₃ H CH₃ c-C₃H₅ CH₂ G4 — 7017 CH₂ CH₃ CH₃ H CH₃ CH₃ CH₂ G5 — 7018CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂ G5 — 7019 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G5 —7020 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ CH₂ G5 — 7021 CH₂ CH₃ CH₃ H CH₃ CH₃ bondG6 — 7022 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G6 — 7023 CH₂ CH₃ CH₃ H CH₃ C₃H₇bond G6 — 7024 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G6 — 7025 CH₂ CH₃ CH₃ H CH₃CH₂═CH bond G7 — 7026 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G8 — 7027 CH₂ CH₃ CH₃ HCH₃ C₂H₅ CH₂ G1 — 7028 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G1 — 7029 CH₂ CH₃ CH₃H CH₃ C₂H₅ CH₂ G2 — 7030 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G2 — 7031 CH₂ Cl ClH H CH₃ bond G1 — 7032 CH₂ Cl Cl H H C₂H₅ bond G1 — 7033 CH₂ Cl Cl H HC₃H₇ bond G1 — 7034 CH₂ Cl Cl H H c-C₃H₅ bond G1 — 7035 CH₂ Cl Cl H HCH₃ bond G2 — 7036 CH₂ Cl Cl H H C₂H₅ bond G2 — 7037 CH₂ Cl Cl H H C₃H₇bond G2 — 7038 CH₂ Cl Cl H H c-C₃H₅ bond G2 — 7039 CH₂ Cl Cl H H CH₃bond G3 — 7040 CH₂ Cl Cl H H C₂H₅ bond G3 — 7041 CH₂ Cl Cl H H C₃H₇ bondG3 — 7042 CH₂ Cl Cl H H c-C₃H₅ bond G3 — 7043 CH₂ Cl Cl H H CH₃ CH₂ G4 —7044 CH₂ Cl Cl H H C₂H₅ CH₂ G4 — 7045 CH₂ Cl Cl H H C₃H₇ CH₂ G4 — 7046CH₂ Cl Cl H H c-C₃H₅ CH₂ G4 — 7047 CH₂ Cl Cl H H CH₃ CH₂ G5 — 7048 CH₂Cl Cl H H C₂H₅ CH₂ G5 — 7049 CH₂ Cl Cl H H C₃H₇ CH₂ G5 — 7050 CH₂ Cl ClH H c-C₃H₅ CH₂ G5 — 7051 CH₂ Cl Cl H H CH₃ bond G6 — 7052 CH₂ Cl Cl H HC₂H₅ bond G6 — 7053 CH₂ Cl Cl H H C₃H₇ bond G6 — 7054 CH₂ Cl Cl H Hc-C₃H₅ bond G6 — 7055 CH₂ Cl Cl H H CH₂═CH bond G7 — 7056 CH₂ Cl Cl H HCH₃ bond G8 — 7057 CH₂ Cl Cl H H C₂H₅ CH₂ G1 — 7058 CH₂ Cl Cl H H C₃H₇CH₂ G1 — 7059 CH₂ Cl Cl H H C₂H₅ CH₂ G2 — 7060 CH₂ Cl Cl H H C₃H₇ CH₂ G2— 7061 CH₂ CH₃ OCH₃ H H CH₃ bond G1 — 7062 CH₂ CH₃ OCH₃ H H C₂H₅ bond G1— 7063 CH₂ CH₃ OCH₃ H H C₃H₇ bond G1 — 7064 CH₂ CH₃ OCH₃ H H c-C₃H₅ bondG1 — 7065 CH₂ CH₃ OCH₃ H H CH₃ bond G2 — 7066 CH₂ CH₃ OCH₃ H H C₂H₅ bondG2 — 7067 CH₂ CH₃ OCH₃ H H C₃H₇ bond G2 — 7068 CH₂ CH₃ OCH₃ H H c-C₃H₅bond G2 — 7069 CH₂ CH₃ OCH₃ H H CH₃ bond G3 — 7070 CH₂ CH₃ OCH₃ H H C₂H₅bond G3 — 7071 CH₂ CH₃ OCH₃ H H C₃H₇ bond G3 — 7072 CH₂ CH₃ OCH₃ H Hc-C₃H₅ bond G3 — 7073 CH₂ CH₃ OCH₃ H H CH₃ CH₂ G4 — 7074 CH₂ CH₃ OCH₃ HH C₂H₅ CH₂ G4 — 7075 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G4 — 7076 CH₂ CH₃ OCH₃ HH c-C₃H₅ CH₂ G4 — 7077 CH₂ CH₃ OCH₃ H H CH₃ CH₂ G5 — 7078 CH₂ CH₃ OCH₃ HH C₂H₅ CH₂ G5 — 7079 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G5 — 7080 CH₂ CH₃ OCH₃ HH c-C₃H₅ CH₂ G5 — 7081 CH₂ CH₃ OCH₃ H H CH₃ bond G6 — 7082 CH₂ CH₃ OCH₃H H C₂H₅ bond G6 — 7083 CH₂ CH₃ OCH₃ H H C₃H₇ bond G6 — 7084 CH₂ CH₃OCH₃ H H c-C₃H₅ bond G6 — 7085 CH₂ CH₃ OCH₃ H H CH₂═CH bond G7 — 7086CH₂ CH₃ OCH₃ H H CH₃ bond G8 oil 7087 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G1 —7088 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G1 — 7089 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G2 —7090 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G2 — 7091 CH₂ Cl OCH₃ H H CH₃ bond G1 —7092 CH₂ Cl OCH₃ H H C₂H₅ bond G1 — 7093 CH₂ Cl OCH₃ H H C₃H₇ bond G1 —7094 CH₂ Cl OCH₃ H H c-C₃H₅ bond G1 — 7095 CH₂ Cl OCH₃ H H CH₃ bond G2 —7096 CH₂ Cl OCH₃ H H C₂H₅ bond G2 — 7097 CH₂ Cl OCH₃ H H C₃H₇ bond G2 —7098 CH₂ Cl OCH₃ H H c-C₃H₅ bond G2 — 7099 CH₂ Cl OCH₃ H H CH₃ bond G3 —7100 CH₂ Cl OCH₃ H H C₂H₅ bond G3 — 7101 CH₂ Cl OCH₃ H H C₃H₇ bond G3 —7102 CH₂ Cl OCH₃ H H c-C₃H₅ bond G3 — 7103 CH₂ Cl OCH₃ H H CH₃ CH₂ G4 —7104 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G4 — 7105 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G4 —7106 CH₂ Cl OCH₃ H H c-C₃H₅ CH₂ G4 — 7107 CH₂ Cl OCH₃ H H CH₃ CH₂ G5 —7108 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G5 — 7109 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G5 —7110 CH₂ Cl OCH₃ H H c-C₃H₅ CH₂ G5 — 7111 CH₂ Cl OCH₃ H H CH₃ bond G6 —7112 CH₂ Cl OCH₃ H H C₂H₅ bond G6 — 7113 CH₂ Cl OCH₃ H H C₃H₇ bond G6 —7114 CH₂ Cl OCH₃ H H c-C₃H₅ bond G6 — 7115 CH₂ Cl OCH₃ H H CH₂═CH bondG7 — 7116 CH₂ Cl OCH₃ H H CH₃ bond G8 oil 7117 CH₂ Cl OCH₃ H H C₂H₅ CH₂G1 — 7118 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G1 — 7119 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G2— 7120 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G2 — 7121 CH₂ Cl CF₃ H H CH₃ bond G1 —7122 CH₂ Cl CF₃ H H C₂H₅ bond G1 — 7123 CH₂ Cl CF₃ H H C₃H₇ bond G1 —7124 CH₂ Cl CF₃ H H c-C₃H₅ bond G1 — 7125 CH₂ Cl CF₃ H H CH₃ bond G2 —7126 CH₂ Cl CF₃ H H C₂H₅ bond G2 — 7127 CH₂ Cl CF₃ H H C₃H₇ bond G2 —7128 CH₂ Cl CF₃ H H c-C₃H₅ bond G2 — 7129 CH₂ Cl CF₃ H H CH₃ bond G3 —7130 CH₂ Cl CF₃ H H C₂H₅ bond G3 — 7131 CH₂ Cl CF₃ H H C₃H₇ bond G3 —7132 CH₂ Cl CF₃ H H c-C₃H₅ bond G3 — 7133 CH₂ Cl CF₃ H H CH₃ CH₂ G4 —7134 CH₂ Cl CF₃ H H C₂H₅ CH₂ G4 — 7135 CH₂ Cl CF₃ H H C₃H₇ CH₂ G4 — 7136CH₂ Cl CF₃ H H c-C₃H₅ CH₂ G4 — 7137 CH₂ Cl CF₃ H H CH₃ CH₂ G5 — 7138 CH₂Cl CF₃ H H C₂H₅ CH₂ G5 — 7139 CH₂ Cl CF₃ H H C₃H₇ CH₂ G5 — 7140 CH₂ ClCF₃ H H c-C₃H₅ CH₂ G5 — 7141 CH₂ Cl CF₃ H H CH₃ bond G6 — 7142 CH₂ ClCF₃ H H C₂H₅ bond G6 — 7143 CH₂ Cl CF₃ H H C₃H₇ bond G6 — 7144 CH₂ ClCF₃ H H c-C₃H₅ bond G6 — 7145 CH₂ Cl CF₃ H H CH₂═CH bond G7 — 7146 CH₂Cl CF₃ H H CH₃ bond G8 oil 7147 CH₂ Cl CF₃ H H C₂H₅ CH₂ G1 — 7148 CH₂ ClCF₃ H H C₃H₇ CH₂ G1 — 7149 CH₂ Cl CF₃ H H C₂H₅ CH₂ G2 — 7150 CH₂ Cl CF₃H H C₃H₇ CH₂ G2 — 7151 CH₂ CF₃ Cl H H CH₃ bond G1 — 7152 CH₂ CF₃ Cl H HC₂H₅ bond G1 — 7153 CH₂ CF₃ Cl H H C₃H₇ bond G1 — 7154 CH₂ CF₃ Cl H Hc-C₃H₅ bond G1 — 7155 CH₂ CF₃ Cl H H CH₃ bond G2 — 7156 CH₂ CF₃ Cl H HC₂H₅ bond G2 — 7157 CH₂ CF₃ Cl H H C₃H₇ bond G2 — 7158 CH₂ CF₃ Cl H Hc-C₃H₅ bond G2 — 7159 CH₂ CF₃ Cl H H CH₃ bond G3 — 7160 CH₂ CF₃ Cl H HC₂H₅ bond G3 — 7161 CH₂ CF₃ Cl H H C₃H₇ bond G3 — 7162 CH₂ CF₃ Cl H Hc-C₃H₅ bond G3 — 7163 CH₂ CF₃ Cl H H CH₃ CH₂ G4 — 7164 CH₂ CF₃ Cl H HC₂H₅ CH₂ G4 — 7165 CH₂ CF₃ Cl H H C₃H₇ CH₂ G4 — 7166 CH₂ CF₃ Cl H Hc-C₃H₅ CH₂ G4 — 7167 CH₂ CF₃ Cl H H CH₃ CH₂ G5 — 7168 CH₂ CF₃ Cl H HC₂H₅ CH₂ G5 — 7169 CH₂ CF₃ Cl H H C₃H₇ CH₂ G5 — 7170 CH₂ CF₃ Cl H Hc-C₃H₅ CH₂ G5 — 7171 CH₂ CF₃ Cl H H CH₃ bond G6 — 7172 CH₂ CF₃ Cl H HC₂H₅ bond G6 — 7173 CH₂ CF₃ Cl H H C₃H₇ bond G6 — 7174 CH₂ CF₃ Cl H Hc-C₃H₅ bond G6 — 7175 CH₂ CF₃ Cl H H CH₂═CH bond G7 — 7176 CH₂ CF₃ Cl HH CH₃ bond G8 — 7177 CH₂ CF₃ Cl H H C₂H₅ CH₂ G1 — 7178 CH₂ CF₃ Cl H HC₃H₇ CH₂ G1 — 7179 CH₂ CF₃ Cl H H C₂H₅ CH₂ G2 — 7180 CH₂ CF₃ Cl H H C₃H₇CH₂ G2 — 7181 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G1 — 7182 CH₂ CH₃ OCH₃ CH₃ HC₂H₅ bond G1 — 7183 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G1 — 7184 CH₂ CH₃ OCH₃CH₃ H c-C₃H₅ bond G1 — 7185 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G2 — 7186 CH₂CH₃ OCH₃ CH₃ H C₂H₅ bond G2 — 7187 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G2 —7188 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G2 — 7189 CH₂ CH₃ OCH₃ CH₃ H CH₃bond G3 — 7190 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ bond G3 — 7191 CH₂ CH₃ OCH₃ CH₃ HC₃H₇ bond G3 — 7192 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G3 — 7193 CH₂ CH₃OCH₃ CH₃ H CH₃ CH₂ G4 — 7194 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G4 — 7195 CH₂CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G4 — 7196 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ CH₂ G4 —7197 CH₂ CH₃ OCH₃ CH₃ H CH₃ CH₂ G5 — 7198 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G5— 7199 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G5 — 7200 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅CH₂ G5 — 7201 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G6 — 7202 CH₂ CH₃ OCH₃ CH₃ HC₂H₅ bond G6 — 7203 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G6 — 7204 CH₂ CH₃ OCH₃CH₃ H c-C₃H₅ bond G6 — 7205 CH₂ CH₃ OCH₃ CH₃ H CH₂═CH bond G7 — 7206 CH₂CH₃ OCH₃ CH₃ H CH₃ bond G8 — 7207 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G1 — 7208CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G1 — 7209 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G2 —7210 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G2 — 7211 O Cl CF₃ H H C₂H₅ CH₂ G1 —7212 O Cl CF₃ H H C₃H₇ CH₂ G1 — 7213 O Cl CF₃ H H C₂H₅ bond G2 — 7214 OCl CF₃ H H C₃H₇ bond G2 — 7215 O Cl CF₃ H H C₂H₅ CH₂ G4 — 7216 CH₂ ClCF₃ H H C₂H₅ CH₂ G1 — 7217 CH₂ Cl CF₃ H H C₃H₇ CH₂ G1 — 7218 CH₂ Cl CF₃H H C₂H₅ bond G2 — 7219 CH₂ Cl CF₃ H H C₃H₇ bond G2 — 7220 CH₂ Cl CF₃ HH C₂H₅ CH₂ G4 — 7221 O CF₃ Cl H H C₂H₅ CH₂ G1 — 7222 O CF₃ Cl H H C₃H₇CH₂ G1 — 7223 O CF₃ Cl H H C₂H₅ bond G2 — 7224 O CF₃ Cl H H C₃H₇ bond G2— 7225 O CF₃ Cl H H C₂H₅ CH₂ G4 — 7226 CH₂ CF₃ Cl H H C₂H₅ CH₂ G1 — 7227CH₂ CF₃ Cl H H C₃H₇ CH₂ G1 — 7228 CH₂ CF₃ Cl H H C₂H₅ bond G2 — 7229 CH₂CF₃ Cl H H C₃H₇ bond G2 — 7230 CH₂ CF₃ Cl H H C₂H₅ CH₂ G4 — 7231 CH₂ CH₃CH₃ H CH₃ C₂H₅ CH₂O G3 oil 7232 CH₂ Cl Cl H H c-C₃H₅ bond G9 — 7233 O ClCl H H c-C₃H₅ bond G9 — 7234 CH₂ Cl CF₃ H H c-C₃H₅ bond G9 oil 7235 O ClCF₃ H H c-C₃H₅ bond G9 — 7236 CH₂ Cl OCH₃ H H c-C₃H₅ bond G9 — 7237 CH₂Cl OCF₃ H H c-C₃H₅ bond G9 — 7238 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G9 —7239 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G9 — 7240 CH₂ CF₃ OCH₃ H H c-C₃H₅ bondG9 — 7241 CH₂ Cl Cl H H c-C₃H₅ bond G10 oil 7242 O Cl Cl H H c-C₃H₅ bondG10 — 7243 CH₂ Cl CF₃ H H c-C₃H₅ bond G10 oil 7244 O Cl CF₃ H H c-C₃H₅bond G10 — 7245 CH₂ Cl OCH₃ H H c-C₃H₅ bond G10 — 7246 CH₂ Cl OCF₃ H Hc-C₃H₅ bond G10 — 7247 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G10 — 7248 CH₂ ClCl H CH₃ c-C₃H₅ bond G10 — 7249 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G10 oil7250 CH₂ Cl Cl H H C₂H₅ bond G10 oil 7251 O Cl Cl H H C₂H₅ bond G10 —7252 CH₂ Cl CF₃ H H C₂H₅ bond G10 98-99 7253 O Cl CF₃ H H C₂H₅ bond G10— 7254 CH₂ Cl OCH₃ H H C₂H₅ bond G10 — 7255 CH₂ Cl OCF₃ H H C₂H₅ bondG10 — 7256 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G10 — 7257 CH₂ Cl Cl H CH₃ C₂H₅bond G10 — 7258 CH₂ CF₃ OCH₃ H H C₂H₅ bond G10 — 7259 CH₂ Cl Cl H H C₃H₇bond G10 oil 7260 O Cl Cl H H C₃H₇ bond G10 — 7261 CH₂ Cl CF₃ H H C₃H₇bond G10 oil 7262 O Cl CF₃ H H C₃H₇ bond G10 — 7263 CH₂ Cl OCH₃ H H C₃H₇bond G10 — 7264 CH₂ Cl OCF₃ H H C₃H₇ bond G10 — 7265 CH₂ CH₃ OCH₃ Cl HC₃H₇ bond G10 — 7266 CH₂ Cl Cl H CH₃ C₃H₇ bond G10 oil 7267 CH₂ CF₃ OCH₃H H C₃H₇ bond G10 — 7268 CH₂ Cl Cl H H C₅H₁₁ bond G10 oil 7269 O Cl Cl HH C₅H₁₁ bond G10 — 7270 CH₂ Cl CF₃ H H C₅H₁₁ bond G10 oil 7271 O Cl CF₃H H C₅H₁₁ bond G10 — 7272 CH₂ Cl OCH₃ H H C₅H₁₁ bond G10 — 7273 CH₂ ClOCF₃ H H C₅H₁₁ bond G10 — 7274 CH₂ CH₃ OCH₃ Cl H C₅H₁₁ bond G10 — 7275CH₂ Cl Cl H CH₃ C₅H₁₁ bond G10 — 7276 CH₂ CF₃ OCH₃ H H C₅H₁₁ bond G10 —7277 CH₂ Cl Cl H H CH₃ CH₂ G10 — 7278 O Cl Cl H H CH₃ CH₂ G10 — 7279 CH₂Cl CF₃ H H CH₃ CH₂ G10 oil 7280 O Cl CF₃ H H CH₃ CH₂ G10 — 7281 CH₂ ClOCH₃ H H CH₃ CH₂ G10 — 7282 CH₂ Cl OCF₃ H H CH₃ CH₂ G10 — 7283 CH₂ CH₃OCH₃ Cl H CH₃ CH₂ G10 — 7284 CH₂ Cl Cl H CH₃ CH₃ CH₂ G10 — 7285 CH₂ CF₃OCH₃ H H CH₃ CH₂ G10 — 7286 CH₂ Cl Cl H H c-C₃H₅ bond G11 oil 7287 O ClCl H H c-C₃H₅ bond G11 — 7288 CH₂ Cl CF₃ H H c-C₃H₅ bond G11 oil 7289 OCl CF₃ H H c-C₃H₅ bond G11 — 7290 CH₂ Cl OCH₃ H H c-C₃H₅ bond G11 — 7291CH₂ Cl OCF₃ H H c-C₃H₅ bond G11 — 7292 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G11— 7293 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G11 — 7294 CH₂ CF₃ OCH₃ H H c-C₃H₅bond G11 — 7295 CH₂ Cl Cl H H C₂H₅ bond G11 oil 7296 O Cl Cl H H C₂H₅bond G11 — 7297 CH₂ Cl CF₃ H H C₂H₅ bond G11 oil 7298 O Cl CF₃ H H C₂H₅bond G11 — 7299 CH₂ Cl OCH₃ H H C₂H₅ bond G11 — 7300 CH₂ Cl OCF₃ H HC₂H₅ bond G11 — 7301 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G11 — 7302 CH₂ Cl Cl HCH₃ C₂H₅ bond G11 — 7303 CH₂ CF₃ OCH₃ H H C₂H₅ bond G11 — 7304 CH₂ Cl ClH H C₃H₇ bond G11 88-89 7305 O Cl Cl H H C₃H₇ bond G11 — 7306 CH₂ Cl CF₃H H C₃H₇ bond G11 oil 7307 O Cl CF₃ H H C₃H₇ bond G11 — 7308 CH₂ Cl OCH₃H H C₃H₇ bond G11 — 7309 CH₂ Cl OCF₃ H H C₃H₇ bond G11 — 7310 CH₂ CH₃OCH₃ Cl H C₃H₇ bond G11 — 7311 CH₂ Cl Cl H CH₃ C₃H₇ bond G11 — 7312 CH₂CF₃ OCH₃ H H C₃H₇ bond G11 — 7313 CH₂ Cl Cl H H C₆H₅ bond G11 156-1577314 O Cl Cl H H C₆H₅ bond G11 — 7315 CH₂ Cl CF₃ H H C₆H₅ bond G11150-151 7316 O Cl CF₃ H H C₆H₅ bond G11 — 7317 CH₂ Cl OCH₃ H H C₆H₅ bondG11 — 7318 CH₂ Cl OCF₃ H H C₆H₅ bond G11 — 7319 CH₂ CH₃ OCH₃ Cl H C₆H₅bond G11 — 7320 CH₂ Cl Cl H CH₃ C₆H₅ bond G11 — 7321 CH₂ CF₃ OCH₃ H HC₆H₅ bond G11 — 7322 CH₂ Cl Cl H H C₂H₅ bond G12 — 7323 O Cl Cl H H C₂H₅bond G12 — 7324 CH₂ Cl CF₃ H H C₂H₅ bond G12 oil 7325 O Cl CF₃ H H C₂H₅bond G12 — 7326 CH₂ Cl OCH₃ H H C₂H₅ bond G12 — 7327 CH₂ Cl OCF₃ H HC₂H₅ bond G12 — 7328 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G12 — 7329 CH₂ Cl Cl HCH₃ C₂H₅ bond G12 — 7330 CH₂ CF₃ OCH₃ H H C₂H₅ bond G12 — 7331 CH₂ Cl ClH H C₃H₇ bond G12 — 7332 O Cl Cl H H C₃H₇ bond G12 — 7333 CH₂ Cl CF₃ H HC₃H₇ bond G12 — 7334 O Cl CF₃ H H C₃H₇ bond G12 — 7335 CH₂ Cl OCH₃ H HC₃H₇ bond G12 — 7336 CH₂ Cl OCF₃ H H C₃H₇ bond G12 — 7337 CH₂ CH₃ OCH₃Cl H C₃H₇ bond G12 — 7338 CH₂ Cl Cl H CH₃ C₃H₇ bond G12 — 7339 CH₂ CF₃OCH₃ H H C₃H₇ bond G12 — 7340 CH₂ Cl Cl H H c-C₃H₅ bond G12 — 7341 O ClCl H H c-C₃H₅ bond G12 — 7342 CH₂ Cl CF₃ H H c-C₃H₅ bond G12 128-1307343 O Cl CF₃ H H c-C₃H₅ bond G12 — 7344 CH₂ Cl OCH₃ H H c-C₃H₅ bond G12— 7345 CH₂ Cl OCF₃ H H c-C₃H₅ bond G12 — 7346 CH₂ CH₃ OCH₃ Cl H c-C₃H₅bond G12 — 7347 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G12 — 7348 CH₂ CF₃ OCH₃ H Hc-C₃H₅ bond G12 — 7349 CH₂ Cl CF₃ H H c-C₃H₅ bond G13 oil 7350 CH₂ Cl ClH H c-C₃H₅ bond G13 — 7351 CH₂ Cl CF₃ H H c-C₃H₅ bond G7 oil 7352 CH₂ ClCl H H c-C₃H₅ bond G7 oil 7353 CH₂ Cl CF₃ H H CH₃ bond G7 — 7354 CH₂ ClCl H H CH₃ bond G7 — 7355 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G7 oil 7356 CH₂CH₃ OCH₃ CH₃ H C₃H₇ bond G7 oil 7357 CH₂ CF₃ OCH₃ H H C₃H₇ bond G7 oil7358 CH₂ CH₃ OCH₃ CH₃ H C₄H₉ bond G7 oil 7359 CH₂ Cl Cl H CH₃ c-C₃H₅bond G7 156-158 7360 CH₂ CF₃ OCH₃ H H CH₃ bond G8 oil 7361 CH₂ CH₃ OCH₃OCH₃ H C₂H₅ bond G10 oil 7362 O Cl Cl H H CH₃ bond G1 — 7363 O Cl CF₃ HH CH₃ bond G1 — 7364 CH₂ Cl OCF₃ H H CH₃ bond G1 — 7365 CH₂ CH₃ OCH₃ ClH CH₃ bond G1 — 7366 CH₂ Cl Cl H CH₃ CH₃ bond G1 — 7367 CH₂ CF₃ OCH₃ H HCH₃ bond G1 — 7368 CH₂ CH₃ OCH₃ F H CH₃ bond G1 — 7369 O Cl Cl H H C₂H₅bond G1 — 7370 O Cl CF₃ H H C₂H₅ bond G1 — 7371 CH₂ Cl OCF₃ H H C₂H₅bond G1 — 7372 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G1 — 7373 CH₂ Cl Cl H CH₃C₂H₅ bond G1 — 7374 CH₂ CF₃ OCH₃ H H C₂H₅ bond G1 — 7375 CH₂ CH₃ OCH₃ FH C₂H₅ bond G1 — 7376 O Cl Cl H H C₃H₇ bond G1 — 7377 O Cl CF₃ H H C₃H₇bond G1 — 7378 CH₂ Cl OCF₃ H H C₃H₇ bond G1 — 7379 CH₂ CH₃ OCH₃ Cl HC₃H₇ bond G1 — 7380 CH₂ Cl Cl H CH₃ C₃H₇ bond G1 — 7381 CH₂ CF₃ OCH₃ H HC₃H₇ bond G1 — 7382 CH₂ CH₃ OCH₃ F H C₃H₇ bond G1 — 7383 O Cl Cl H Hc-C₃H₅ bond G1 — 7384 O Cl CF₃ H H c-C₃H₅ bond G1 — 7385 CH₂ Cl OCF₃ H Hc-C₃H₅ bond G1 — 7386 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G1 — 7387 CH₂ Cl ClH CH₃ c-C₃H₅ bond G1 — 7388 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G1 — 7389 CH₂CH₃ OCH₃ F H c-C₃H₅ bond G1 — 7390 CH₂ Cl CF₃ H H c-C₃H₅ bond G14 oil7391 CH₂ Cl Cl H H c-C₃H₅ bond G14 — 7391 CH₂ Cl CF₃ H H c-C₃H₅ bond G15oil 7392 CH₂ Cl Cl H H c-C₃H₅ bond G15 — 7393 CH₂ Cl CF₃ H H c-C₃H₅ bondG16 139-140 7394 CH₂ Cl Cl H H c-C₃H₅ bond G16 — 7395 CH₂ Cl CF₃ H Hc-C₃H₅ bond G17 — 7396 CH₂ Cl Cl H H c-C₃H₅ bond G17 oil 7397 CH₂ Cl CF₃H H c-C₃H₅ bond G18 — 7398 CH₂ Cl Cl H H c-C₃H₅ bond G18 oil 7399 CH₂ ClCl H CH₃ CH₃ bond G8 oil 7400 CH₂ Cl CF₃ H H c-C₃H₅ bond G19 — 7401 CH₂Cl Cl H H c-C₃H₅ bond G19 oil 7402 CH₂ Cl Cl H H c-C₃H₅ bond G20 oil7403 CH₂ Cl CF₃ H H c-C₃H₅ bond G20 — 7404 CH₂ Cl Cl H H C₄H₉ bond G1oil 7405 CH₂ Cl Cl H H C₆H₅ C═O C₆H₅ oil 7406 CH₂ Cl Cl H H C₆H₅ C═O G21oil 7407 CH₂ Cl Cl H H C₆H₅ C═O G22 oil 7408 CH₂ Cl Cl H H 4-F— C═O CH₃oil C₆H₄CH₂ 7409 CH₂ Cl Cl H H c-C₃H₅ bond G23 oil Key: (a) G groups:

G7 = CH═CH₂ G8 = E-CH═CH—CH₃

G10 = —C≡CH G11 = —C≡CCH₃

(b) Where a compound is indicated as an “oil”, spectral data is providedas follows: Example 7056 spectral data: MS (ESI): m/e 363 (M+2), 361(M⁺, 100%). Example 7086 spectral data: TLC R_(F) 0.25 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.91 (1H, s), 7.72 (1H, d, J= 9.2 Hz), 6.90-6.84 (2H, m), 6.08 (1H, ddq, J = 15.4 Hz, 6.6H, 1.4 Hz),5.67 (1H, dqd, J = 15.4 Hz, 6.5H, 1.5 Hz), 5.24 (1H, br pentet, J = 7.0Hz), 3.85 (3H, s), 2.96 (2H, dq, J = 7.5, 1.1 Hz), 2.47 (3H, s), 1.81(3H, d, J = 7.0 Hz), 1.73 (3H, dt, J = 6.2, 1.3 Hz), 1.41 (3H, t, J =7.5 Hz). MS (NH₃—CI): m/e 339 (3), 338 (23), 337 (100). Example 7116spectral data: TLC R_(F) 0.15 (30:70 ethyl acetate-hexane). ¹H NMR (300MHz, CDCl₃): δ 8.96 (1H, s), 7.68 (1H, d, J = 8.4 Hz), 7.09 (1H, d, J =2.6 Hz), 6.96 (1H, dd, J = 8.4, 2.6 Hz), 6.09 (1H, ddq, J = 15.4 Hz,6.6H, 1.8 Hz), 5.67 (1H, dqd, J = 15.4 Hz, 6.5H, 1.4 Hz), 5.23 (1H, brpentet, J = 6.8 Hz), 3.87 (3H, s), 2.98 (2H, q, J = 7.5 Hz), 1.82 (3H,d, J = 7.0 Hz), 1.73 (3H, dt, J = 6.6, 1.3 Hz), 1.40 (3H, t, J = 7.5Hz). MS (NH₃—CI): m/e 360 (7), 359 (33), 358 (23), 357 (100). Example7145 spectral data: m.p. 78-79° C. TLC R_(F) 0.52 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H, s), 7.86-7.81 (2H,m), 7.68 (1H, d, J = 8.0 Hz), 6.38 (2H, ddd, J = 17.2 Hz, 10.6H, 5.8Hz), 5.90-5.83 (1H, m), 5.40 (2H, dd, J = 10.6, 1.3 Hz), 5.29 (2H, dt, J= 17.2, 0.9 Hz), 2.97 (2H, q, J = 7.6 Hz), 1.41 (3H, t, J = 7.6 Hz). MS(NH₃—CI): m/e 396 (8), 395 (36), 394 (25), 393 (100). Analysiscalculated for C₁₉H₁₆ClF₃N₄: C, 58.10; H, 4.12; N, 14.26; found: C,58.14; H, 4.28; N, 13.74. Example 7146 spectral data: TLC R_(F) 0.43(30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99 (1H, s),7.84-7.79 (2H, m), 7.67 (1H, dd, J = 8.5, 1.1 Hz), 6.10 (1H, ddq, J =15.4 Hz, 6.8H, 1.8 Hz), 5.70 (1H, dqd, J = 15.4 Hz, 6.5H, 1.1 Hz), 5.24(1H, pentet, J = 7.0 Hz), 2.99 (2H, q, J = 7.5 Hz), 1.83 (3H, d, J = 7.0Hz), 1.74 (3H, dt, J = 6.6, 1.3 Hz), 1.40 (3H, t, J = 7.5 Hz). MS(NH₃—CI): m/e 398 (7), 397 (36), 396 (25), 395 (100). Example 7231spectral data: m.p. 78-88° C. TLC R_(F) 0.55 (50:50 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): Major isomer: δ 8.90 (1H, s),6.95 (2H, s), 4.68-3.05 (6H, m), 3.02-2.92 (2H, m), 2.70-2.55 (2H, m),2.32 (3H, s), 2.20-2.00 (2H, m), 2.05 (3H, s), 1.96 (3H, s), 1.70-1.45(4H, m), 1.39 (3H, t, J = 7.7 Hz), 0.93 (3H, t, J = 7.3 Hz); Minorisomer: δ 8.89 (1H, s), 6.95 (2H, s), 4.68-3.05 (6H, m), 3.02-2.92 (2H,m), 2.70-2.55 (2H, m), 2.32 (3H, s), 2.20-2.00 (2H, m), 2.06 (3H, s),2.01 (3H, s), 1.70-1.45 (4H, m), 1.38 (3H, t, J = 7.7 Hz), 0.90 (3H, t,J = 7.3 Hz). MS (NH₃—CI): m/e calc'd for C₂₅H₃₅N₄O₂: 423.2760, found423.2748; 425 (5), 424 (29), 423 (100). Analysis calc'd forC₂₅H₃₄N₄O₂.H₂O: C, 68.15; H, 8.24; N, 12.72; found: C, 67.80; H, 7.89;N, 12.24. Example 7234 spectral data: TLC R_(F) 0.46 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99 (1H, s), 7.87 (1H, d, J= 8.0 Hz), 7.83 (1H, s), 7.68 (1H, d, J = 8.0 Hz), 6.50 (1H, d, J = 3.0Hz), 5.99 (1H, d, J = 3.0 Hz), 5.10 (1H, d, J = 10.6 Hz), 2.99-2.79 (2H,m), 2.20 (3H, s), 2.10-2.00 (1H, m), 1.30 (3H, t, J = 7.5 Hz), 1.00-0.90(1H, m), 0.71- 0.59 (2H, m), 0.56-0.46 (1H, m). MS (NH₃—CI): m/e 463(35), 461 (100). Example 7241 spectral data: MS (NH₃—CI): m/e 371 (M+H⁺,100%). Example 7243 spectral data: TLC R_(F) 0.43 (30:70 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H, s), 7.85 (1H, d, J= 8.0 Hz), 7.83 (1H, s), 7.69 (1H, d, J = 8.0 Hz), 5.24 (1H, dd, J =8.4, 2.5 Hz), 3.28 (1H, dq, J = 15.5, 7.5 Hz), 3.14 (1H, dq, J = 15.5,7.5 Hz), 2.56 (1H, d, J = 2.5 Hz), 1.78-1.67 (1H, m), 1.48 (3H, t, J =7.5 Hz), 0.92-0.81 (2H, m), 0.66-0.49 (2H, m). MS (NH₃—CI): m/ecalculated for C₂₀H₁₇ClF₃N₄: 405.1094, found 405.1098; 408 (8), 407(34), 406 (25), 405 (100). Example 7249 spectral data: TLC R_(F) 0.19(30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.93 (1H, s),7.72 (1H, d, J = 8.5 Hz), 7.37 (1H, d, J = 2.5 Hz), 7.18 (1H, dd, J =8.5, 2.5 Hz), 5.23 (1H, dd, J = 8.1, 2.6 Hz), 3.92 (3H, s), 3.31-3.04(2H, m), 2.54 (1H, d, J = 2.6 Hz), 1.76-1.64 (1H, m), 1.47 (3H, t, J =7.5 Hz), 0.90-0.80 (2H, m), 0.64- 0.52 (2H, m). MS (NH₃—CI): m/e calc'dfor C₂₁H₂₀F₃N₄O: 401.1603, found 401.1602; 403 (6), 402 (24), 401 (100).Example 7250 spectral data: TLC R_(F) 0.17 (20:80 ethyl acetate-hexane).¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H, s), 7.67 (1H, d, J = 8.5 Hz), 7.58(1H, d, J = 1.8 Hz), 7.41 (1H, dd, J = 8.5, 1.8 Hz), 5.53 (1H, dt, J =8.0, 2.6 Hz), 3.20 (1H, dq, J = 15.8, 7.5 Hz), 3.05 (1H, dq, J = 15.8,7.5 Hz), 2.55 (1H, d, J = 2.6 Hz), 2.42-2.29 (1H, m), 2.28-2.15 (1H, m),1.46 (3H, t, J = 7.5 Hz), 1.04 (3H, t, J = 7.5 Hz). MS (NH₃—CI): m/ecalc'd for C₁₈H₁₇Cl₂N₄: 359.0830, found 359.0835; 364 (2), 363 (12), 362(14), 361 (67), 360 (24), 359 (100). Example 7259 spectral data: TLCR_(F) 0.22 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.01(1H, s), 7.67 (1H, d, J = 8.1 Hz), 7.58 (1H, d, J = 1.8 Hz), 7.40 (1H,dd, J = 8.1, 1.8 Hz), 5.63 (1H, dt, J = 7.9, 2.5 Hz), 3.20 (1H, dq, J =15.7, 7.7 Hz), 3.05 (1H, dq, J = 15.7, 7.7 Hz), 2.54 (1H, d, J = 2.5Hz), 2.37-2.24 (1H, m), 2.19-2.06 (1H, m), 1.60-1.45 (1H, m), 1.46 (3H,t, J = 7.7 Hz), 1.39-1.25 (1H, m), 0.99 (3H, t, J = 7.3 Hz). MS(NH₃—CI): m/e calc'd for C₁₉H₁₉Cl₂N₄: 373.0987, found 373.0984; 378 (3),377 (12), 376 (15), 375 (66), 374 (26), 373 (100). Example 7261 spectraldata: TLC R_(F) 0.52 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz,CDCl₃): δ 9.03 (1H, s), 7.84 (2H, m), 7.68 (1H, dd, J = 7.3, 0.7 Hz),5.65 (1H, dt, J = 8.1, 2.6 Hz), 3.24-3.02 (2H, m), 2.55 (1H, d, J = 2.6Hz), 2.33-2.25 (1H, m), 2.20-2.12 (1H, m), 1.46 (3H, t, J = 7.5 Hz),1.00 (3H, t, J = 7.3 Hz). MS (NH₃—CI): m/e calc'd for C₂₀H₁₉ClF₃N₄:407.1250, found 407.1243, 410 (8), 409 (36), 408 (25), 407 (100).Example 7266 spectral data: TLC R_(F) 0.19 (20:80 ethyl acetate-hexane).¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H, d, J = 1.5 Hz), 7.38 (1H, d, J =1.8 Hz), 7.24 (1H, d, J = 1.8 Hz), 5.70-5.58 (1H, m), 3.24-3.00 (2H, m),2.55 (1H, d, J = 2.5 Hz), 2.40-2.25 (1H, m), 2.20-2.05 (1H, m), 2.10(3H, d, J = 1.8 Hz), 1.62-1.47 (1H, m), 1.43 (3H, t, J = 7.5 Hz), 1.42-1.27 (1H, m), 1.00 (3H, t, J = 7.3 Hz). MS (NH₃—CI): m/e calc'd forC₂₀H₂₁Cl₂N₄: 387.1143, found 387.1144; 392 (3), 391 (12), 390 (16), 389(66), 388 (27), 387 (100). Example 7268 spectral data: TLC R_(F) 0.29(20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H, s),7.67 (1H, d, J = 8.5 Hz), 7.58 (1H, d, J = 2.2 Hz), 7.41 (1H, dd, J =8.5, 2.2 Hz), 5.60 (1H, dt, J = 7.9, 2.6 Hz), 3.19 (1H, dq, J = 15.3,7.3 Hz), 3.05 (1H, dq, J = 15.3, 7.3 Hz), 2.54 (1H, d, J = 2.6 Hz),2.38-2.23 (1H, m), 2.20-2.05 (1H, m), 1.58-1.44 (1H, m), 1.46 (3H, t, J= 7.3 Hz), 1.40-1.23 (5H, m), 0.87 (3H, t, J = 7.0 Hz). MS (NH₃—CI): m/ecalc'd for C₂₁H₂₃Cl₂N₄: 401.1300, found 401.1300; 406 (3), 405 (13), 404(17), 403 (69), 402 (28), 401 (100). Example 7270 spectral data: TLCR_(F) 0.60 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.03(1H, s), 7.84 (2H, m), 7.68 (1H, dd, J = 9.1, 0.7 Hz), 5.62 (1H, dt, J =8.1, 2.6 Hz), 3.24-3.02 (2H, m), 2.55 (1H, d, J = 2.6 Hz), 2.34-2.27(1H, m), 2.19-2.13 (1H, m), 1.46 (3H, t, J = 7.3 Hz), 1.40-1.25 (6H, m),0.88 (3H, t, J = 7.0 Hz). MS (NH₃—CI): m/e calc'd for C₂₂H₂₃ClF₃N₄:435.1563, found 435.1566; 438 (9), 437 (36), 436 (27), 435 (100).Example 7279 spectral data: TLC R_(F) 0.31 (30:70 ethyl acetate-hexane).¹H NMR (300 MHz, CDCl₃): δ 8.97 (1H, s), 7.84 (2H, m), 7.68 (1H, d, J =7.7 Hz), 4.74-4.67 (1H, m), 3.45-3.36 (1H, m), 3.03 (2H, q, J = 7.7 Hz),3.00-2.93 (1H, m), 1.93 (1H, t, J = 2.7 Hz), 1.86 (3H, d, J = 7.0 Hz),1.43 (3H, t, J = 7.5 Hz). MS (NH₃—CI): m/e 396 (7), 395 (34), 394 (24),393 (100). Example 7286 spectral data: TLC R_(F) 0.29 (20:80 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.97 (1H, s), 7.68 (1H, d, J= 8.4 Hz), 7.58 (1H, d, J = 1.8 Hz), 7.41 (1H, dd, J = 8.4, 1.8 Hz),5.19 (1H, dq, J = 8.4, 2.6 Hz), 3.26 (1H, dq, J = 15.7, 7.3 Hz), 3.14(1H, dq, J = 15.7, 7.3 Hz), 1.88 (3H, d, J = 2.6 Hz), 1.70-1.60 (1H, m),1.47 (3H, t, J = 7.3 Hz), 0.89-0.78 (2H, m), 0.60-0.43 (2H, m). MS(NH₃—CI): m/e calc'd for C₂₀H₁₉Cl₂N₄: 385.0986, found 385.0992; 390 (3),389 (12), 388 (15), 387 (66), 386 (26), 385 (100). Example 7288 spectraldata: MS (NH₃—CI): m/e 419 (M+H⁺, 100%). Example 7295 spectral data: TLCR_(F) 0.19 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99(1H, s), 7.67 (1H, d, J = 8.4 Hz), 7.57 (1H, d, J = 2.2 Hz), 7.40 (1H,dd, J = 8.4, 2.2 Hz), 5.49 (1H, tq, J = 7.7, 2.2 Hz), 3.19 (1H, dq, J =15.3, 7.7 Hz), 3.05 (1H, dq, J = 15.3, 7.7 Hz), 2.26 (1H, dq, J = 21.3,7.7 Hz), 2.13 (1H, dq, J = 21.3, 7.7 Hz), 1.87 (3H, d, J = 2.2 Hz), 1.45(3H, t, J = 7.7 Hz), 1.01 (3H, t, J = 7.7 Hz). MS (NH₃—CI): m/e calc'dfor C₁₉H₁₉Cl₂N₄: 373.0987, found 373.0987; 378 (3), 377 (13), 376 (15),375 (68), 374 (25), 373 (100). Example 7297 spectral data: TLC R_(F)0.48 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 9.01 (1H,s), 7.83 (2H, m), 7.67 (1H, dd, J = 7.4, 0.8 Hz), 5.51 (1H, dt, J = 8.1,2.2 Hz), 3.25-3.03 (2H, m), 2.35- 2.13 (2H, m), 1.88 (3H, d, J = 2.2Hz), 1.45 (3H, t, J = 7.5 Hz), 1.01 (3H, t, J = 7.3 Hz). MS (NH₃—CI):m/e calc'd for C₂₀H₁₉ClF₃N₄: 407.1250, found 407.1267; 410 (8), 409(35), 408 (25), 407 (100). Example 7306 spectral data: MS (NH₃—CI): m/e421 (M+H⁺, 100%). Example 7324 spectral data: TLC R_(F) 0.38 (30:70ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99 (1H, s), 7.84(1H, d, J = 8.4 Hz), 7.83 (1H, d, J = 1.8 Hz), 7.68 (1H, dd, J = 8.4,1.8 Hz), 7.36 (1H, d, J = 3 Hz), 6.51 (1H, d, J = 5 Hz), 6.39 (1H, dd, J= 5, 3 Hz), 5.78 (1H, dd, J = 9, 7 Hz), 3.00-2.85 (2H, m), 2.75-2.52(2H, m), 1.37 (3H, t, J = 7.5 Hz), 0.98 (3H, t, J = 7.5 Hz). MS(NH₃—CI): m/e 439 (1), 438 (8), 437 (34), 436 (26), 435 (100). Example7349 spectral data: TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): δ 9.00 (1H, s), 7.87 (1H, d, J = 8.0 Hz), 7.83 (1H,s), 7.69 (1H, d, J = 8.0 Hz), 5.01 (1H, d, J = 10.6 Hz), 2.93 (1H, dq, J= 15.9, 7.5 Hz), 2.75 (1H, dq, J = 15.9, 7.5 Hz), 2.58 (3H, s), 2.04-1.94 (1H, m), 1.93 (3H, s), 1.33 (3H, t, J = 7.5 Hz), 1.32-1.22 (1H, m),1.00-0.87 (1H, m), 0.74-0.60 (3H, m). MS (NH₃—CI): m/e calculated forC₂₃H₂₂ClF₃N₅O: 476.1465, found 476.1469; 478 (35), 476 (100). Example7351 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR(300 MHz, CDCl₃): δ 8.99 (1H, s), 7.88-7.82 (2H, m), 7.68 (1H, d, J =8.0 Hz), 6.35 (1H, ddd, J = 17.2 Hz, 10.6H, 5.1 Hz), 5.33 (1H, br d, J =10.6 Hz), 5.26 (1H, br d, J = 17.2 Hz), 4.43-4.37 (1H, m), 3.02-2.90(2H, m), 1.99-1.89 (1H, m), 1.41 (3H, t, J = 7.5 Hz), 0.94-0.84 (1H, m),0.62-0.52 (2H, m), 0.40-0.30 (1H, m). MS (NH₃—CI): m/e 411 (1), 410 (7),409 (34), 408 (25), 407 (100). Example 7352 spectral data: TLC R_(F)0.13 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.96 (1H,s), 7.69 (1H, d, J = 8.4 Hz), 7.58 (1H, d, J = 2.2 Hz), 7.41 (1H, dd, J= 8.8, 2.2 Hz), 6.33 (1H, ddd, J = 17.2, 10.6, 5.2 Hz), 5.35-5.20 (2H,m), 4.42-4.35 (1H, m), 3.03-2.88 (2H, m), 2.00-1.89 (1H, m), 1.40 (3H,t, J = 7.6 Hz), 0.92-0.82 (1H, m), 0.62- 0.52 (2H, m), 0.40-0.30 (1H,m). MS (NH₃—CI): m/e calc'd for C₁₉H₁₉Cl₂N₄: 373.1000, found 373.0995;378 (3), 377 (12), 376 (15), 375 (66), 374 (26), 373 (100). Example 7355spectral data: MS (NH₃—CI): m/e 337 (M+H⁺, 100%). Example 7356 spectraldata: MS (NH₃—CI): m/e 365 (M+H⁺, 100%). Example 7357 spectral data: TLCR_(F) 0.19 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.91(1H, s), 7.70 (1H, d, J = 8.4 Hz), 7.35 (1H, d, J = 2.6 Hz), 7.19 (1H,dd, J = 8.4, 2.6 Hz), 6.42 (1H, ddd, J = 16.9, 10.3, 6.6 Hz), 5.27 (1H,d, J = 10.2 Hz), 5.14 (1H, d, J = 17.3 Hz), 5.08-4.99 (1H, m), 3.91 (3H,s), 2.99-2.90 (2H, m), 2.42-2.29 (1H, m), 2.27-2.15 (1H, m), 1.39 (3H,t, J = 7.5 Hz), 1.38-1.10 (2H, m), 0.95 (3H, t, J = 7.1 Hz). MS(NH₃—CI): m/e calc'd for C₂₁H₂₄F₃N₄O: 405.1915, found 405.1923; 407 (5),406 (24), 405 (100). Analysis calc'd for C₂₁H₂₃F₃N₄O: C, 62.37; H, 5.73;N, 13.85; found: C, 62.42; H, 5.73; N, 13.48. Example 7358 spectraldata: MS (NH₃—CI): m/e 379 (M+H⁺, 100%). Example 7360 spectral data: TLCR_(F) 0.13 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.91(1H, s), 7.68 (1H, d, J = 8.8 Hz), 7.35 (1H, d, J = 2.6 Hz), 7.16 (1H,dd, J = 8.8, 2.6 Hz), 6.15-6.05 (1H, m), 5.73- 5.63 (1H, m), 5.28-5.18(1H, m), 3.91 (3H, s), 2.96 (2H, q, J = 7.4 Hz), 1.82 (3H, d, J = 7.3Hz), 1.74 (3H, dt, J = 6.6, 1.3 Hz), 1.39 (3H, t, J = 7.4 Hz). MS(NH₃—CI): m/e calc'd for C₂₀H₂₂F₃N₄O: 391.1733, found 391.1736; 393 (3),392 (23), 391 (100). Example 7361 spectral data: TLC R_(F) 0.43 (50:50ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.96 (1H, s), 7.42(1H, s), 6.84 (1H, s), 5.55 (1H, dt, J = 5.5, 2.2 Hz), 3.94 (3H, s),3.92 (3H, s), 3.49-2.98 (2H, m), 2.54 (1H, d, J = 2.6 Hz), 2.45 (3H, s),2.35-2.16 (2H, m), 1.48 (3H, t, J = 7.5 Hz), 1.03 (3H, t, J = 7.5 Hz),MS (NH₃—CI): m/e calc'd for C₂₁H₂₅N₄O₂: 365.1978, found 365.1966; 367(6), 366 (24), 365 (100). Example 7390 spectral data: TLC R_(F) 0.45(30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99 (1H, s),7.88 (1H, d, J = 8.0 Hz), 7.83 (1H, s), 7.69 (1H, d, J = 8.0 Hz),7.30-7.22 (1H, m), 7.07-7.01 (1H, m), 6.99-6.92 (1H, m), 5.25 (1H, d, J= 10.2 Hz), 2.97-2.78 (2H, m), 2.23 (1H, br), 1.32 (3H, t, J = 7.3 Hz),1.10-1.00 (1H, m), 0.81-0.71 (1H, m), 0.64-0.54 (1H, m), 0.50-0.40 (1H,m). MS (NH₃—CI): m/e calc'd for C₂₂H₁₉ClF₃N₄S: 463.0971, found 463.0960;467 (3), 466 (10), 465 (99), 464 (28), 463 (100). Example 7392 spectraldata: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz,CDCl₃): δ 8.99 (1h, s), 7.88 (1H, d, J = 8.0 Hz), 7.83 (1H, s), 7.68(1H, d, J = 8.0 Hz), 7.30 (1H, br d, J = 4.8 Hz), 7.18 (1H, br d, J =4.8 Hz), 6.92 (1H, m), 5.12 (1H, d, J = 9.9 Hz), 2.92-2.67 (2H, m), 2.13(1H, br), 1.28 (3H, t, J = 7.5 Hz), 1.08-0.99 (1H, m), 0.79- 0.69 (1H,m), 0.55-0.45 (2H, m). MS (NH₃—CI): m/e calculated for C₂₂H₁₉ClF₃N₄S:463.0971, found 463.0953; 467 (3), 466 (10), 465 (39), 464 (29), 463(100). Example 7396 spectral data: TLC R_(F) 0.27 (20:80 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.96 (1H, s), 7.67 (1H, d, J= 8.1 Hz), 7.58 (1H, d, J = 1.8 Hz), 7.41 (1H, dd, J = 8.1, 1.8 Hz),6.86 (1H, s), 5.83 (1H, dd, J = 9.9, 6.2 Hz), 4.43 (2H, q, J = 7.3 Hz),2.98 (2H, q, J = 7.7 Hz), 2.91-2.78 (1H, m), 2.63-2.49 (1H, m), 1.42(3H, t, J = 7.7 Hz), 1.40 (3H, t, J = 7.3 Hz), 1.39-1.19 (2H, m), 1.00(3H, t, J = 7.3 Hz). MS (NH₃—CI): m/e calc'd for C₂₃H₂₄Cl₂N₅O₃:488.1256, found 488.1252; 493 (3), 492 (13), 491 (18), 490 (68), 489(28), 488 (100). Example 7398 spectral data: TLC R_(F) 0.11 (20:80 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.99 (1H, s), 7.72 (1H, d, J= 8.1 Hz), 7.59 (1H, d, J = 1.8 Hz), 7.42 (1H, dd, J = 8.1, 1.8 Hz),5.40 (1H, dd, J = 10.4, 5.0 Hz), 4.42 (2H, q, J = 7.4 Hz), 3.00-2.90(2H, m), 2.66-2.52 (1H, m), 2.51-2.38 (1H, m), 1.46 (3H, t, J = 7.4 Hz),1.41 (3H, t, J = 7.3 Hz), 1.40-1.10 (2H, m), 0.98 (3H, t, J = 7.2 Hz).MS (NH₃—CI): m/e calc'd for C₂₄H₂₅Cl₂N₆O₄: 531.1315, found 531.1315; 531(100). Example 7399 spectral data: TLC R_(F) 0.13 (20:80 ethylacetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ 8.98 (1H, s), 7.38 (1H, d, J= 1.8 Hz), 7.23 (1H, d, J = 1.8 Hz), 6.15-6.06 (1H, m), 5.76-5.63 (1H,m), 5.26-5.20 (1H, m), 2.96 (2H, q, J = 7.4 Hz), 2.10 (3H, s), 1.83 (3H,d, J = 7.0 Hz), 1.74 (3H, d, J = 6.6 Hz), 1.37 (3H, t, J = 7.4 Hz). MS(NH₃—CI): m/e calc'd for C₁₉H₂₁Cl₂N₄: 375.1117, found 375.1123; 380 (2),379 (12), 378 (15), 377 (66), 376 (26), 375 (100). Example 7401 spectraldata: TLC R_(F) 0.20 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): δ 8.99(1H, s), 7.71 (1H, d, J = 8.4 Hz), 7.58 (1H, d, J = 1.8 Hz), 7.41 (1H,dd, J = 8.4, 1.8 Hz), 7.11 (1H, d, J = 1.1 Hz), 6.87 (1H, d, J = 1.1Hz), 5.41 (1H, d, J = 10.3 Hz), 3.34 (3H, s), 3.08 (1H, dq, J = 15.8,7.7 Hz), 2.89 (1H, dq, J = 15.8, 7.7 Hz), 2.39-2.25 (1H, m), 1.14 (3H,t, J = 7.7 Hz), 1.07-0.97 (1H, m), 0.70-0.58 (2H, m), 0.52- 0.42 (1H,m). MS (NH₃—CI): m/e calc'd for C₂₁H₂₁Cl₂N₆: 427.1205, found 427.1196;429 (66), 427 (100). Example 7402 spectral data: MS (NH₃—CI): m/e 424(M+H⁺, 100%). Example 7404 spectral data: MS (NH₃—CI): m/e 419 (M+H⁺,100%). Example 7405 spectral data: MS (NH₃—CI): m/e 487 (M+H⁺, 100%).Example 7406 spectral data: MS (NH₃—CI): m/e 501 (M+H⁺, 100%). Example7407 spectral data: MS (NH₃—CI): m/e 517 (M+H⁺, 100%). Example 7408spectral data: MS (NH₃—CI): m/e 457 (M+H⁺, 100%). Example 7409 spectraldata: MS (NH₃—CI): m/e 429 (M+H⁺, 100%).

Utility CRF-1 Receptor Binding Assay for the Evaluation of BiologicalActivity

The following is a description of the isolation of cell membranescontaining cloned human CRF-1 receptors for use in the standard bindingassay as well as a description of the assay itself.

Messenger RNA was isolated from human hippocampus. The mRNA was reversetranscribed using oligo (dt) 12-18 and the coding region was amplifiedby PCR from start to stop codons The resulting PCR fragment was clonedinto the EcoRV site of PGEMV, from whence the insert was reclaimed usingXhoI+XbaI and cloned into the XhoI+XbaI sites of vector pm3ar (whichcontains a CMV promoter, the SV40 ‘t’ splice and early poly A signals,an Epstein-Barr viral origin of replication, and a hygromycin selectablemarker). The resulting expression vector, called phchCRFR wastransfected in 293EBNA cells and cells retaining the episome wereselected in the presence of 400 mM hygromycin. Cells surviving 4 weeksof selection in hygromycin were pooled, adapted to growth in suspensionand used to generate membranes for the binding assay described below.Individual aliquots containing approximately 1×10⁸ of the suspendedcells were then centrifuged to form a pellet and frozen.

For the binding assay a frozen pellet described above containing 293EBNAcells transfected with hCRFR1 receptors is homogenized in 10 mL of icecold tissue buffer (50 mM HEPES buffer pH 7.0, containing 10 mM MgCl₂, 2mM EGTA, 1 mg/L aprotinin, 1 mg/mL leupeptin and 1 mg/mL pepstatin). Thehomogenate is centrifuged at 40,000×g for 12 min and the resultingpellet rehomogenized in 10 mL of tissue buffer. After anothercentrifugation at 40,000×g for 12 min, the pellet is resuspended to aprotein concentration of 360 mg/mL to be used in the assay.

Binding assays are performed in 96 well plates; each well having a 300mL capacity. To each well is added 50 mL of test drug dilutions (finalconcentration of drugs range from 10⁻¹⁰ to 10⁻⁵ M), 100 mL of¹²⁵I-ovine-CRF (¹²⁵I-o-CRF) (final concentration 150 pM) and 150 mL ofthe cell homogenate described above. Plates are then allowed to incubateat room temperature for 2 hours before filtering the incubate over GF/Ffilters (presoaked with 0.3% polyethyleneimine) using an appropriatecell harvester. Filters are rinsed 2 times with ice cold assay bufferbefore removing individual filters and assessing them for radioactivityon a gamma counter.

Curves of the inhibition of ¹²⁵I-o-CRF binding to cell membranes atvarious dilutions of test drug are analyzed by the iterative curvefitting program LIGAND [P. J. Munson and D. Rodbard, Anal. Biochem.107:220 (1980), which provides K_(i) values for inhibition which arethen used to assess biological activity.

Alternatively, tissues and cells which naturally express CRF receptorscan be employed in binding assays analogous to those described above.

A compound is considered to be active if it has a K_(i) value of lessthan about 10000 nM for the inhibition of CRF.

Inhibition of CRF-Stimulated Adenylate Cyclase Activity

Inhibition of CRF-stimulated adenylate cyclase activity can be performedas described by G. Battaglia et al. Synapse 1:572 (1987). Briefly,assays are carried out at 37° C. for 10 min in 200 mL of buffercontaining 100 mM Tris-HCl (pH 7.4 at 37° C.), 10 mM MgCl₂, 0.4 mM EGTA,0.1% BSA, 1 mM isobutylmethylxanthine (IBMX), 250 units/mLphosphocreatine kinase, 5 mM creatine phosphate, 100 mM guanosine5′-triphosphate, 100 nM oCRF, antagonist peptides (concentration range10⁻⁹ to 10⁻⁶ M) and 0.8 mg original wet weight tissue (approximately40-60 mg protein). Reactions are initiated by the addition of 1 mMATP/³²P]ATP (approximately 2-4 mCi/tube) and terminated by the additionof 100 mL of 50 mM Tris-HCL, 45 mM ATP and 2% sodium dodecyl sulfate. Inorder to monitor the recovery of cAMP, 1 mL of [³H]cAMP (approximately40,000 dpm) is added to each tube prior to separation. The separation of[³²p] cAMP from [³²P]ATP is performed by sequential elution over Dowexand alumina columns.

In Vivo Biological Assay

The in vivo activity of the compounds of the present invention can beassessed using any one of the biological assays available and acceptedwithin the art. Illustrative of these tests include the Acoustic StartleAssay, the Stair Climbing Test, and the Chronic Administration Assay.These and other models useful for the testing of compounds of thepresent invention have been outlined in C. W. Berridge and A. J. DunnBrain Research Reviews 15:71 (1990). Compounds may be tested in anyspecies of rodent or small mammal.

Compounds of this invention have utility in the treatment of inbalancesassociated with abnormal levels of corticotropin releasing factor inpatients suffering from depression, affective disorders, and/or anxiety.

Compounds of this invention can be administered to treat theseabnormalities by means that produce contact of the active agent with theagent's site of action in the body of a mammal. The compounds can beadministered by any conventional means available for use in conjunctionwith pharmaceuticals either as individual therapeutic agent or incombination of therapeutic agents. They can be administered alone, butwill generally be administered with a pharmaceutical carrier selected onthe basis of the chosen route of administration and standardpharmaceutical practice.

The dosage administered will vary depending on the use and known factorssuch as pharmacodynamic character of the particular agent, and its modeand route of administration; the recipient's age, weight, and health;nature and extent of symptoms; kind of concurrent treatment; frequencyof treatment; and desired effect. For use in the treatment of saiddiseases or conditions, the compounds of this invention can be orallyadministered daily at a dosage of the active ingredient of 0.002 to 200mg/kg of body weight. Ordinarily, a dose of 0.01 to 10 mg/kg in divideddoses one to four times a day, or in sustained release formulation willbe effective in obtaining the desired pharmacological effect.

Dosage forms (compositions) suitable for administration contain fromabout 1 mg to about 100 mg of active ingredient per unit. In thesepharmaceutical compositions, the active ingredient will ordinarily bepresent in an amount of about. 0.5 to 95% by weight based on the totalweight of the composition.

The active ingredient can be administered orally is solid dosage forms,such as capsules, tablets and powders; or in liquid forms such aselixirs, syrups, and/or suspensions. The compounds of this invention canalso be administered parenterally in sterile liquid dose formulations.

Gelatin capsules can be used to contain the active ingredient and asuitable carrier such as but not limited to lactose, starch, magnesiumstearate, steric acid, or cellulose derivatives. Similar diluents can beused to make compressed tablets. Both tablets and capsules can bemanufactured as sustained release products to provide for continuousrelease of medication over a period of time. Compressed tablets can besugar-coated or film-coated to mask any unpleasant taste, or used toprotect the active ingredients from the atmosphere, or to allowselective disintegration of the tablet in the gastrointestinal tract.

Liquid dose forms for oral administration can contain coloring orflavoring agents to increase patient acceptance.

In general, water, pharmaceutically acceptable oils, saline, aqueousdextrose (glucose), and related sugar solutions and glycols, such aspropylene glycol or polyethylene glycol, are suitable carriers forparenteral solutions. Solutions for parenteral administration preferablycontain a water soluble salt of the active ingredient, suitablestabilizing agents, and if necessary, butter substances. Antioxidizingagents, such as sodium bisulfite, sodium sulfite, or ascorbic acid,either alone or in combination, are suitable stabilizing agents. Alsoused are citric acid and its salts, and EDTA. In addition, parenteralsolutions can contain preservatives such as benzalkonium chloride,methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in “Remington'sPharmaceutical Sciences”, A. Osol, a standard reference in the field.

Useful pharmaceutical dosage-forms for administration of the compoundsof this invention can be illustrated as follows:

Capsules

A large number of units capsules are prepared by filling standardtwo-piece hard gelatin capsules each with 100 mg of powdered activeingredient, 150 mg lactose, 50 mg cellulose, and 6 mg magnesiumstearate.

Soft Gelatin Capsules

A mixture of active ingredient in a digestible oil such as soybean,cottonseed oil, or olive oil is prepared and injected by means of apositive displacement was pumped into gelatin to form soft gelatincapsules containing 100 mg of the active ingredient. The capsules werewashed and dried.

Tablets

A large number of tablets are prepared by conventional procedures sothat the dosage unit was 100 mg active ingredient, 0.2 mg of colloidalsilicon dioxide, 5 mg of magnesium stearate, 275 mg of microcrystallinecellulose, 11 mg of starch, and 98.8 mg lactose. Appropriate coatingsmay be applied to increase palatability or delayed adsorption.

The compounds of this invention may also be used as reagents orstandards in the biochemical study of neurological function,dysfunction, and disease.

Although the present invention has been described and exemplified interms of certain preferred embodiments, other embodiments will beapparent to those skilled in the art. The invention is, therefore, notlimited to the particular embodiments described and exemplified, but iscapable of modification or variation without departing from the spiritof the invention, the full scope of which is delineated by the appendedclaims.

What is claimed is:
 1. A method of treating a disorder selected fromaffective disorder, anxiety, depression, headache, irritable bowelsyndrome, post-traumatic stress disorder, supranuclear palsy, immunesuppression, Alzheimer's disease, gastrointestinal diseases, anorexianervosa or other feeding disorder, drug addiction, drug or alcoholwithdrawal symptoms, inflammatory diseases, cardiovascular orheart-related diseases, fertility problems, human immunodeficiency virusinfections, hemorrhagic stress, obesity, infertility, head and spinalcord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis,and hypoglycemia in mammals, comprising: administering to the mammal atherapeutically effective amount of a compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein: A is N and B is C—R⁸ or A is C—R⁷ and B is N; D is an aryl orheteroaryl group attached through an unsaturated carbon atom; X isselected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond; n is 0, 1or 2; R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b); R¹ is substitutedwith 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b),—COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂,—NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a),1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl,wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a groupselected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—,—NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl issubstituted with 0-1 substituents selected from the group R^(13a),CO₂R^(14b), COR^(14b) and SO₂R^(14b); R¹ is also substituted with 0-3substituents independently selected at each occurrence from the groupR^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl,F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₄ alkoxy-C₁₋₄alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—; provided that R¹ isother than: (a) a 3-cyclopropyl-3-methoxypropyl group; (b) anunsubstituted-(alkoxy)methyl group; and, (c) a 1-hydroxyalkyl group;also provided that when R¹ is alkyl substituted with OH, then the carbonin the R¹ adjacent to the ring N is other than CH₂; R^(1a) is aryl andis selected from the group phenyl, naphthyl, indanyl and indenyl, eachR^(1a) being substituted with 0-5 substituents independently selected ateach occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F,I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷,—OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a),—NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a); R^(1b) isheteroaryl and is selected from the group pyridyl, pyrimidinyl,triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl,thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl,benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogenatom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b),COR^(14b) and SO₂R^(14b); R^(1c) is heterocyclyl and is a saturated orpartially saturated heteroaryl, each heterocyclyl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a),—OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂,—NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and—CONR^(13a)R^(16a) and each heterocyclyl being substituted on anynitrogen atom with 0-1 substituents selected from the group R^(13a),CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom isoptionally monooxidized or dioxidized; R² is selected from the groupC₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and issubstituted with 0-3 substituents selected from the group —CN, hydroxy,halo and C₁₋₄ alkoxy; alternatively R², in the case where X is a bond,is selected from the group —CN, CF₃ and C₂F₅; R³, R⁷ and R⁸ areindependently selected at each occurrence from the group H, Br, Cl, F,I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groupsselected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and (C₁₋₄alkyl)₂amino; provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, thenR³ is other than substituted or unsubstituted phenyl; R⁹ and R¹⁰ areindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl; R¹³ is selected from thegroup H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)—,heteroaryl and heteroaryl(C₁₋₄ alkyl)—; R^(13a) and R^(16a) areindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆cycloalkyl-C₁₋₆ alkyl; R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆alkyl, aryl, aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)—and benzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl andbenzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁵is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl,nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino; R^(15a) isindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁷ is selected at eachoccurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄ haloalkyl,R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl; R¹⁸ and R¹⁹ areindependently selected at each occurrence from the group H, C₁₋₆ alkyl,C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl,and C₁₋₄ haloalkyl; alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) takentogether form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl; aryl is independently selected at each occurrencefrom the group phenyl, naphthyl, indanyl and indenyl, each aryl beingsubstituted with 0-5 substituents independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy,C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂,—NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1phenyl, each phenyl substituent being substituted with 0-4 substituentsselected from the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN,dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; and, heteroaryl isindependently selected at each occurrence from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl,tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂,—NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).
 2. Amethod according to claim 1, wherein the compound is of formula Ia:


3. A method according to claim 1, wherein the compound is of formula Ib:


4. The method of claim 1, wherein said disorder is anxiety, depression,anorexia nervosa, irritable bowel syndrome, drug or alcohol withdrawalsymptoms, inflammation, or stroke.
 5. A method of treating a disorderinduced or facilitated by CRF in a mammal, comprising administering tosaid mammal a therapeutically effective amount of a compound of formula(I):

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein: A is N and B is C—R⁸ or A is C—R⁷ and B is N; D is an aryl orheteroaryl group attached through an unsaturated carbon atom; X isselected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond; n is 0, 1or 2; R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b); R¹ is substitutedwith 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b),—COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂,—NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a),1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl,wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a groupselected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—,—NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl issubstituted with 0-1 substituents selected from the group R^(13a),CO₂R^(14b), COR^(14b) and SO₂R^(14b); R¹ is also substituted with 0-3substituents independently selected at each occurrence from the groupR^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl,F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₄ alkoxy-C₁₋₄alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—; provided that R¹ isother than: (a) a 3-cyclopropyl-3-methoxypropyl group; (b) anunsubstituted-(alkoxy)methyl group; and, (c) a 1-hydroxyalkyl group;also provided that when R¹ is alkyl substituted with OH, then the carbonin the R¹ adjacent to the ring N is other than CH₂; R^(1a) is aryl andis selected from the group phenyl, naphthyl, indanyl and indenyl, eachR^(1a) being substituted with 0-5 substituents independently selected ateach occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F,I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷,—OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a),—NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a); R^(1b) isheteroaryl and is selected from the group pyridyl, pyrimidinyl,triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl,thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl,benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl,tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted on 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂,—NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and—CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogenatom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b),COR^(14b) and SO₂R^(14b); R^(1c) is heterocyclyl and is a saturated orpartially saturated heteroaryl, each heterocyclyl being substituted on0-4 carbon atoms with a substituent independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I,C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a),—OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂,—NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and—CONR^(13a)R^(16a) and each heterocyclyl being substituted on anynitrogen atom with 0-1 substituents selected from the group R^(13a),CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom isoptionally monooxidized or dioxidized; R² is selected from the groupC₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and issubstituted with 0-3 substituents selected from the group —CN, hydroxy,halo and C₁₋₄ alkoxy; alternatively R², in the case where X is a bond,is selected from the group —CN, CF₃ and C₂F₅; R³, R⁷ and R⁸ areindependently selected at each occurrence from the group H, Br, Cl, F,I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groupsselected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and (C₁₋₄alkyl)₂amino; provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, thenR³ is other than substituted or unsubstituted phenyl; R⁹ and R¹⁰ areindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl; R¹³ is selected from thegroup H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)—,heteroaryl and heteroaryl(C₁₋₄ alkyl)—; R^(13a) and R^(16a) areindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆cycloalkyl-C₁₋₆ alkyl; R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆alkyl, aryl, aryl(C₁₋₄ alkyl)—, heteroaryl and heteroaryl(C₁₋₄ alkyl)—and benzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, r, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl andbenzyl, each benzyl being substituted on the aryl moiety with 0-1substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁵is independently selected at each occurrence from the group H, C₁₋₄alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl,each phenyl or benzyl being substituted on the aryl moiety with 0-3groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl,nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino; R^(15a) isindependently selected at each occurrence from the group H, C₁₋₄ alkyl,C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁷ is selected at eachoccurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄ haloalkyl,R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl; R¹⁸ and R¹⁹ areindependently selected at each occurrence from the group H, C₁₋₆ alkyl,C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl,and C₁₋₄ haloalkyl; alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) takentogether form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;R^(17a) and R^(19a) are independently selected at each occurrence fromthe group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyland C₁₋₄ haloalkyl; aryl is independently selected at each occurrencefrom the group phenyl, naphthyl, indanyl and indenyl, each aryl beingsubstituted with 0-5 substituents independently selected at eachoccurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy,C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂,SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂,—NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl,each phenyl substituent being substituted with 0-4 substituents selectedfrom the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN,dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; and, heteroaryl isindependently selected at each occurrence from the group pyridyl,pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl,imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl,benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl,tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl,2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide,indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, eachheteroaryl being substituted 0-4 carbon atoms with a substituentindependently selected at each occurrence from the group C₁₋₆ alkyl,C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH,—S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂,—NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and eachheteroaryl being substituted on any nitrogen atom with 0-1 substituentsselected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).